an-alkali-burn-injury-model-of-corneal-neovascularization-in-the-mouse

An Alkali-burn Injury Model of Corneal Neovascularization in the Mouse

Under normal conditions, the cornea is avascular, and this transparency is essential for maintaining good visual acuity. Neovascularization (NV) of the ...

Tulane University

Dopaminergic (DA) neurons in the substantia nigra play crucial roles in movement control and other physiological activities. Degeneration of these neurons is closely associated with Parkinson's disease. However, the molecular identity of nigral DA neurons is not fully understood. To identify nigral DA neuron-enriched genes, we used microarrays to compare the genome-wide gene expression profiles in 6-hydroxydopamine-lesioned, and control, substantia nigra. We identified a total of 88 unique differentially expressed gene transcripts. The spatial expression patterns of a set of these genes, including Slc10a4, Rit2, F2r, Snx10 and Slc24a3, were validated by in situ hybridization. It was revealed that their expression was highly specific in the substantia nigra. Thus we identified a set of genes that are highly expressed in nigral DA neurons, and may be involved in the maintenance and survival of nigral DA neurons in the adult rat brain. Our study also provides a general approach for profiling cell type-specific gene expression in the mature mammalian brain.

Identification of nigral dopaminergic neuron-enriched genes in adult rats.

&#x4EE5;&#x524D;&#x7684;&#x7279;&#x70B9; bystin &#x6837; (BYSL) &#x57FA;&#x56E0;&#x7F16;&#x7801;&#x8F85;&#x52A9;&#x86CB;&#x767D;&#x53C2;&#x4E0E;&#x65E9;&#x671F;&#x80DA;&#x80CE;&#x690D;&#x5165;&#x7684;&#x7EC6;&#x80DE;&#x7C98;&#x9644;&#x3002;&#x5B83;&#x8FD8;&#x53C2;&#x4E0E; 40S &#x6838;&#x7CD6;&#x4F53;&#x4E9A;&#x57FA;&#x751F;&#x7269;&#x53D1;&#x751F;&#x548C;&#x88AB;&#x53D1;&#x73B0;&#x5728;&#x8FC5;&#x901F;&#x6210;&#x957F;&#x7684;&#x80DA;&#x80CE;&#x548C;&#x80BF;&#x7624;&#x7EC6;&#x80DE;&#x682A;&#x8868;&#x8FBE;&#x3002;&#x4E3A;&#x4E86;&#x63A2;&#x7D22; BYSL &#x5728;&#x80BF;&#x7624;&#x7EC6;&#x80DE;&#x589E;&#x6B96;&#x548C;&#x751F;&#x957F;&#x7684;&#x4F5C;&#x7528;&#xFF0C;&#x6211;&#x4EEC;&#x7528;&#x809D;&#x7EC6;&#x80DE;&#x764C; (HCC) &#x4F5C;&#x4E3A;&#x4E00;&#x79CD;&#x6A21;&#x5F0F;&#x3002;&#x5728;&#x8FD9;&#x91CC;&#xFF0C;&#x6211;&#x4EEC;&#x62A5;&#x544A; BYSL &#x662F;&#x4F53;&#x5916;&#x548C;&#x4F53;&#x5185;&#x809D;&#x764C;&#x7EC6;&#x80DE;&#x751F;&#x957F;&#x7684;&#x5173;&#x952E;&#x3002;BYSL &#x57FA;&#x56E0;&#x548C;&#x4EBA;&#x7C7B;&#x809D;&#x764C;&#x6807;&#x672C;&#x4E2D;&#x7684;&#x86CB;&#x767D;&#x8868;&#x8FBE;&#x6C34;&#x5E73;&#x660E;&#x663E;&#x589E;&#x52A0;&#x4E86;&#x76F8;&#x6BD4;&#x4E0E;&#x76F8;&#x90BB;&#x975E;&#x764C;&#x7EC4;&#x7EC7;&#x4E2D;&#x770B;&#x5230;&#x7684;&#x90A3;&#x4E9B;&#x3002;&#x4F53;&#x5916;&#xFF0C;BYSL &#x7684;&#x77ED;&#x53D1;&#x5939; RNA &#x7684;&#x6291;&#x5236;&#x4F5C;&#x7528;&#x964D;&#x4F4E;&#x809D;&#x764C;&#x7EC6;&#x80DE;&#x589E;&#x6B96;&#x3001; &#x8BF1;&#x5BFC;&#x7EC6;&#x80DE;&#x51CB;&#x4EA1;&#x548C;&#x90E8;&#x5206;&#x88AB;&#x6355;&#x5728; G2/M &#x671F;&#x7684;&#x7EC6;&#x80DE;&#x5468;&#x671F;&#x3002;&#x4F53;&#x5185;&#xFF0C;&#x809D;&#x764C;&#x7EC6;&#x80DE;&#x6CBB;&#x7597; BYSL siRNA &#x5931;&#x8D25;&#x5230;&#x7A97;&#x4F53;&#x80BF;&#x7624;&#x88F8;&#x9F20;&#x76AE;&#x4E0B;&#x690D;&#x5165;&#x672F;&#x540E;&#x3002;&#x82E5;&#x8981;&#x786E;&#x5B9A; BYSL RNAi &#x8BF1;&#x5BFC;&#x7EC6;&#x80DE;&#x751F;&#x957F;&#x902E;&#x6355;&#x3001; BYSL &#x4E9A;&#x7EC6;&#x80DE;&#x5B9A;&#x4F4D;&#x5728;&#x6709;&#x4E1D;&#x5206;&#x88C2;&#x4E2D;&#x7684;&#x7EC6;&#x80DE;&#x57FA;&#x7840;&#x548C; interphase HepG2 &#x7EC6;&#x80DE;&#x88AB;&#x5BA1;&#x67E5;&#x3002;BYSL nucleologenesis&#xFF0C;&#x5728;&#x7EC6;&#x80DE;&#x6709;&#x4E1D;&#x5206;&#x88C2;&#x671F;&#x95F4;&#x5305;&#x62EC;&#x6838;&#x4EC1;&#x6D3E;&#x751F;&#x7076; (NDF)&#x3001; perichromosomal &#x5730;&#x533A;&#x548C; prenucleolar &#x6B63;&#x6587; &#xFF08;&#x5E03;&#x9686;&#x8FEA;&#x56FD;&#x5BB6;&#x8B66;&#x5BDF;&#xFF09; &#x671F;&#x95F4;&#x51FA;&#x5E2D;&#x591A;&#x4E2A;&#x9636;&#x6BB5;&#x4E86;&#x3002;BYSL &#x6D88;&#x8017;&#x663E;&#x8457;&#x538B;&#x5236; NDF &#x548C;&#x5E03;&#x9686;&#x8FEA;&#x56FD;&#x5BB6;&#x8B66;&#x5BDF;&#x5F62;&#x6210;&#x548C;&#x6270;&#x4E71;&#x6838;&#x4EC1;&#x88C5;&#x914D;&#x540E;&#x6709;&#x4E1D;&#x5206;&#x88C2;&#xFF0C;&#x589E;&#x52A0;&#x7EC6;&#x80DE;&#x51CB;&#x4EA1;&#x8FC7;&#x7A0B;&#x4E2D;&#x4EA7;&#x751F;&#x548C;&#x51CF;&#x5C11;&#x5BF9;&#x8840;&#x6E05;&#x9965;&#x997F;&#x7684;&#x8010;&#x53D7;&#x6027;&#x809D;&#x764C;&#x7EC6;&#x80DE;&#x3002;&#x4E24;&#x8005;&#x5408;&#x8BA1;&#xFF0C;&#x6211;&#x4EEC;&#x7684;&#x7814;&#x7A76;&#x8868;&#x660E; BYSL &#x8868;&#x8FBE;&#x4E0A;&#x8C03;&#x5728;&#x809D;&#x764C;&#x53D1;&#x751F;&#x4E2D;&#x8D77;&#x7740;&#x4F5C;&#x7528;&#x3002;

Bystin &#x6837;&#x86CB;&#x767D;&#x662F;&#x5728;&#x809D;&#x7EC6;&#x80DE;&#x764C;&#x7684;&#x4E0A;&#x8C03;&#x548C;&#x6240;&#x9700;&#x7684; nucleologenesis &#x5728;&#x80BF;&#x7624;&#x7EC6;&#x80DE;&#x589E;&#x6B96;&#x3002;

The bystin-like (BYSL) gene was previously characterized to encode an accessory protein for cell adhesion that participates in early embryo implantation. It is also involved in 40S ribosomal subunit biogenesis and is found to be expressed in rapidly growing embryo and cancer cell lines. In order to explore the role of BYSL in cancer cell proliferation and growth, we used hepatocellular carcinoma (HCC) as a model. Here, we report that BYSL is crucial for HCC cell growth both in vitro and in vivo. Expression levels of BYSL mRNA and protein in human HCC specimens were markedly increased compared with those seen in adjacent non-cancerous tissue. In vitro, inhibition of BYSL by short hairpin RNA decreased HCC cell proliferation, induced apoptosis and partially arrested the cell cycle in the G2/M phase. In vivo, HCC cells treated with BYSL siRNA failed to form tumors in nude mice after subcutaneous implantation. To determine the cellular basis for BYSL RNAi-induced cell growth arrest, BYSL subcellular localization in mitotic and interphase HepG2 cells was examined. BYSL was present at multiple stages during nucleologenesis, including in nucleolus-derived foci (NDF), perichromosomal regions and the prenucleolar body (PNB) during mitosis. BYSL depletion remarkably suppressed NDF and PNB formation, and disrupted nucleoli assembly after mitosis, resulting in increased apoptosis and reduced tolerance of HCC cells to serum starvation. Taken together, our studies indicate that upregulated BYSL expression plays a role in hepatocarcinogenesis.

Bystin-like protein is upregulated in hepatocellular carcinoma and required for nucleologenesis in cancer cell proliferation.

Le g&egrave;ne bystin (BYSL) a &eacute;t&eacute; caract&eacute;ris&eacute; ant&eacute;rieurement pour coder une prot&eacute;ine d&#39;adh&eacute;sion cellulaire qui participe &agrave; l&#39;implantation d&#39;embryon pr&eacute;coce. Il est aussi impliqu&eacute; dans la biogen&egrave;se de sous-unit&eacute; ribosomique 40 s et se trouve &agrave; s&#39;exprimer dans l&#39;embryon et le cancer des lign&eacute;es de cellules &agrave; croissance rapide. Afin d&#39;explorer le r&ocirc;le de BYSL dans la croissance et la prolif&eacute;ration des cellules canc&eacute;reuses, nous avons utilis&eacute; le carcinome h&eacute;patocellulaire (CHC) comme un mod&egrave;le. Ici, nous rapportons que BYSL est crucial pour la croissance cellulaire in vitro et in vivo HCC. Niveaux d&#39;expression des ARNm BYSL et de prot&eacute;ines dans des &eacute;chantillons humains de HCC ont nettement augment&eacute;s compar&eacute; avec ceux observ&eacute;s dans les tissus adjacents non canc&eacute;reuses. In vitro, l&#39;inhibition de la BYSL par l&#39;ARN en &eacute;pingle &agrave; cheveux courts diminue la prolif&eacute;ration des cellules HCC, induit l&#39;apoptose et partiellement arr&ecirc;t&eacute; le cycle cellulaire en phase G2/M. In vivo, cellules HCC trait&eacute;es avec le siARN BYSL a &eacute;chou&eacute; &agrave; former des tumeurs chez la souris nude apr&egrave;s implantation sous-cutan&eacute;e. Pour d&eacute;terminer la base cellulaire pour l&#39;arr&ecirc;t de la croissance cellulaire induite par l&#39;ARNi BYSL, localisation sous-cellulaire BYSL en mitose et interphase cellules HepG2 a &eacute;t&eacute; examin&eacute;e. BYSL assista &agrave; plusieurs stades au cours de la nucleologenesis, y compris dans les foyers d&eacute;riv&eacute; de nucl&eacute;ole (NDF), r&eacute;gions de perichromosomal et le corps pr&eacute;nucl&eacute;olaires (PNB) au cours de la mitose. Appauvrissement de BYSL remarquablement supprim&eacute;e formation NDF et PNB et perturb&eacute; l&#39;Assembl&eacute;e nucl&eacute;oles apr&egrave;s la mitose, ce qui entra&icirc;ne une apoptose accrue et r&eacute;duit la tol&eacute;rance des cellules de la HCC &agrave; la privation de s&eacute;rum. Ensemble, nos &eacute;tudes indiquent que l&#39;expression BYSL surexprim&eacute;s joue un r&ocirc;le dans hepatocarcinogenesis.

Bystin-comme la prot&eacute;ine est augment&eacute;e dans le carcinome h&eacute;patocellulaire et requis pour nucleologenesis dans la prolif&eacute;ration des cellules canc&eacute;reuses.

Das Bystin-wie (BYSL) Gen zeichnete sich zuvor um ein Zubeh&ouml;r-Protein f&uuml;r Zelladh&auml;sion zu codieren, die in fr&uuml;hen Embryo-Implantation beteiligt ist. Er engagiert sich auch in den 40er Jahren ribosomal Untereinheit Biogenese und findet sich in schnell wachsenden Embryo und Krebs-Zelllinien ausgedr&uuml;ckt werden. Um die Rolle der BYSL in Krebs Zellproliferation und Wachstum zu erforschen, haben wir das Hepatozellul&auml;re Karzinom (HCC) als Modell verwendet. Hier berichten wir, dass BYSL entscheidend f&uuml;r HCC-Zellwachstum in vitro und in vivo. Ausdruck waren BYSL mRNA und Protein in Proben menschlichen HCC deutlich im Vergleich mit denen in benachbarten nicht-Krebsgewebe gesehen zugenommen. In vitro Hemmung der BYSL durch kurze Haarnadel RNA verringert HCC Zellproliferation, Apoptose induziert und teilweise in der G2/M-Phase des Zellzyklus verhaftet. In vivo konnte HCC Zellen mit BYSL SiRNA behandelten Form Tumoren in den nude M&auml;usen nach subkutaner Implantation. Um festzustellen, die zellul&auml;re Grundlage f&uuml;r BYSL RNAi-induced Zelle Wachstum Verhaftung, BYSL subzellulare Lokalisation in mitotische und interphase HepG2-Zellen wurde untersucht. BYSL war in mehreren Phasen w&auml;hrend der Nucleologenesis, einschlie&szlig;lich im Nukleolus abgeleitete Herde (NDF), Perichromosomal-Regionen und den prenucleolar K&ouml;rper (PNB) w&auml;hrend der Mitose. BYSL Ersch&ouml;pfung bemerkenswert NDF und PNB Formation, unterdr&uuml;ckte und Kernk&ouml;rperchen Assembly nach Mitose, was zu erh&ouml;hten Apoptose gest&ouml;rt und reduzierte Toleranz der HCC-Zellen zu einer Serum-Hungersnot. Zusammen genommen, zufolge unsere Studien herraufreguliert BYSL Ausdruck im Hepatocarcinogenesis eine Rolle spielt.

Bystin-Like Protein ist herraufreguliert in das Hepatozellul&auml;re Karzinom und f&uuml;r Nucleologenesis in Krebs Zellproliferation notwendig.

Il gene (BYSL) bystin-come in precedenza &egrave; stato caratterizzato per codificare una proteina accessoria per l&#39;adesione delle cellule che partecipa l&#39;annidamento dell&#39;embrione precoce. Esso &egrave; anche coinvolto nella biogenesi subunit&agrave; ribosomiale 40S e si trova ad essere espresso in linee di cellule di embrione e cancro in rapida crescita. Al fine di esplorare il ruolo di BYSL in crescita e la proliferazione di cellule cancerogene, abbiamo usato il carcinoma epatocellulare (HCC) come un modello. Riportiamo qui, che BYSL &egrave; fondamentale per la crescita di cellule HCC in vitro e in vivo. I livelli di espressione del mRNA BYSL e di proteine in campioni umani HCC erano nettamente aumentati rispetto con quelli osservati nei tessuti adiacenti non-cancerosi. In vitro, l&#39;inibizione della BYSL da short hairpin RNA ridotta proliferazione delle cellule HCC, induce apoptosi e parzialmente arrestato il ciclo cellulare nella fase G2/M. In vivo, le cellule HCC trattate con siRNA BYSL Impossibile i tumori nei topi nudi forma dopo l&#39;impianto sottocutaneo. &Egrave; stati esaminati per determinare la base cellulare per arresto di sviluppo il RNAi-indotta delle cellule, localizzazione sottocellulare BYSL in mitosi e l&#39;interfase cellule HepG2. BYSL era presente in pi&ugrave; fasi durante nucleologenesis, compresi nelle foci nucleolo-derivato (NDF), perichromosomal regioni e del corpo prenucleolar (PNB) durante la mitosi. BYSL esaurimento notevolmente soppressa formazione NDF e PNB e perturbato Assemblea nucleoli dopo la mitosi, con conseguente aumentata apoptosi e ridotta tolleranza delle cellule HCC alla fame di siero. Presi insieme, i nostri studi indicano che espressione BYSL sovraregolati gioca un ruolo in hepatocarcinogenesis.

Bystin-come proteina &egrave; sovraregolati nel carcinoma epatocellulare e necessaria per nucleologenesis nella proliferazione di cellule cancerogene.

&#x30DE;&#x30FC;&#x30AF; stin &#x69D8; (BYSL) &#x907A;&#x4F1D;&#x5B50;&#x306F;&#x521D;&#x671F;&#x80DA;&#x306E;&#x7740;&#x5E8A;&#x306B;&#x53C2;&#x52A0;&#x3059;&#x308B;&#x7D30;&#x80DE;&#x63A5;&#x7740;&#x306E;&#x30A2;&#x30AF;&#x30BB;&#x30B5;&#x30EA;&#x30FC;&#x306E;&#x30BF;&#x30F3;&#x30D1;&#x30AF;&#x8CEA;&#x306F;&#x3001;&#x30A8;&#x30F3;&#x30B3;&#x30FC;&#x30C9;&#x3059;&#x308B;&#x4EE5;&#x524D;&#x7279;&#x5FB4;&#x3065;&#x3051;&#x3089;&#x308C;&#x307E;&#x3057;&#x305F;&#x3002;&#x305D;&#x308C;&#x3082; 40 &#x4EE3; subunit &#x751F;&#x5408;&#x6210;&#x306B;&#x95A2;&#x4E0E;&#x3057;&#x3066;&#x3044;&#x308B;&#x3057;&#x3001;&#x80DA;&#x3068;&#x764C;&#x306E;&#x30BB;&#x30EB;&#x30E9;&#x30A4;&#x30F3;&#x3092;&#x6025;&#x901F;&#x306B;&#x6210;&#x9577;&#x3057;&#x3066;&#x3067;&#x8868;&#x73FE;&#x3055;&#x308C;&#x308B;&#x3053;&#x3068;&#x304C;&#x308F;&#x304B;&#x3063;&#x305F;&#x3002;&#x764C;&#x7D30;&#x80DE;&#x306E;&#x5897;&#x6B96;&#x3068;&#x6210;&#x9577;&#x306B;&#x304A;&#x3051;&#x308B; BYSL &#x306E;&#x5F79;&#x5272;&#x3092;&#x63A2;&#x308B;&#x305F;&#x3081;&#x3001;&#x809D;&#x7D30;&#x80DE;&#x764C; (HCC) &#x3092;&#x30E2;&#x30C7;&#x30EB;&#x3068;&#x3057;&#x3066;&#x4F7F;&#x7528;&#x3055;&#x308C;&#x307E;&#x3059;&#x3002;&#x3053;&#x3053;&#x3067;&#x306F;&#x3001;BYSL &#x304C;&#x809D;&#x7D30;&#x80DE;&#x764C;&#x7D30;&#x80DE;&#x306E;&#x6210;&#x9577;&#x3092; in vitro &#x304A;&#x3088;&#x3073; in vivo &#x3067;&#x91CD;&#x8981;&#x3067;&#x3042;&#x308B;&#x3053;&#x3068;&#x3092;&#x5831;&#x544A;&#x3057;&#x307E;&#x3059;&#x3002;&#x5F0F;&#x30EC;&#x30D9;&#x30EB;&#x306E; BYSL mRNA &#x3068;&#x30BF;&#x30F3;&#x30D1;&#x30AF;&#x8CEA;&#x3072;&#x3068;&#x809D;&#x7D30;&#x80DE;&#x764C;&#x6A19;&#x672C;&#x3067;&#x8457;&#x3057;&#x304F;&#x306B;&#x6BD4;&#x3079;&#x3066;&#x304C;&#x96A3;&#x63A5;&#x3059;&#x308B;&#x975E;&#x764C;&#x6027;&#x30C6;&#x30A3;&#x30C3;&#x30B7;&#x30E5;&#x3067;&#x898B;&#x3089;&#x308C;&#x308B;&#x5897;&#x52A0;&#x3057;&#x305F;.In vitro &#x306E;&#x6291;&#x5236; BYSL &#x77ED;&#x9396;&#x30D8;&#x30A2;&#x30D4;&#x30F3;&#x578B; RNA &#x306B;&#x3088;&#x308B;&#x809D;&#x7D30;&#x80DE;&#x5897;&#x6B96;&#x3092;&#x6E1B;&#x5C11;&#x3001;&#x30A2;&#x30DD;&#x30C8;&#x30FC;&#x30B7;&#x30B9;&#x8A98;&#x5C0E;&#x3057;&#x3001;G2/M &#x76F8;&#x306E;&#x7D30;&#x80DE;&#x5468;&#x671F;&#x3092;&#x90E8;&#x5206;&#x7684;&#x306B;&#x902E;&#x6355;&#x3002;In vivo BYSL siRNA &#x306E;&#x809D;&#x7D30;&#x80DE;&#x30D5;&#x30A9;&#x30FC;&#x30E0;&#x816B;&#x760D;&#x306E;&#x30CC;&#x30FC;&#x30C9;&#x30DE;&#x30A6;&#x30B9;&#x76AE;&#x4E0B;&#x6CE8;&#x5165;&#x5F8C;&#x3067;&#x3057;&#x305F;&#x3002;BYSL RNAi &#x304C;&#x8A98;&#x5C0E;&#x3059;&#x308B;&#x7D30;&#x80DE;&#x5897;&#x6B96;&#x505C;&#x6B62;, BYSL &#x306E;&#x7D30;&#x80DE;&#x5185;&#x5C40;&#x5728;&#x7D30;&#x80DE;&#x5206;&#x88C2;&#x306E;&#x305F;&#x3081;&#x306E;&#x7D30;&#x80DE;&#x306E;&#x57FA;&#x790E;&#x3092;&#x6C7A;&#x5B9A;&#x3057;&#x3001;&#x4E2D;&#x9593;&#x671F;&#x306E; HepG2 &#x7D30;&#x80DE;&#x3092;&#x691C;&#x8A0E;&#x3057;&#x305F;.BYSL &#x6838;&#x5C0F;&#x4F53;&#x7531;&#x6765;&#x5DE3; (NDF)&#x3001;perichromosomal &#x5730;&#x57DF;&#x3001;prenucleolar &#x4F53; &#xFF08;PNB&#xFF09; &#x306E;&#x6709;&#x7CF8;&#x5206;&#x88C2;&#x306E;&#x9593;&#x3092;&#x542B;&#x3080; nucleologenesis &#x306E;&#x4E2D;&#x306B;&#x8907;&#x6570;&#x306E;&#x6BB5;&#x968E;&#x3067;&#x5B58;&#x5728;&#x3057;&#x3066;&#x3044;&#x305F;&#x3002;&#x975E;&#x5E38;&#x306B; BYSL &#x67AF;&#x6E07; NDF &#x304A;&#x3088;&#x3073; PNB &#x306E;&#x751F;&#x6210;&#x306F;&#x6291;&#x5236;&#x3057;&#x30A2;&#x30DD;&#x30C8;&#x30FC;&#x30B7;&#x30B9;&#x306B;&#x4F34;&#x3046;&#x6838;&#x5C0F;&#x4F53;&#x30A2;&#x30BB;&#x30F3;&#x30D6;&#x30EA;&#x6709;&#x7CF8;&#x5206;&#x88C2;&#x5F8C;&#x304C;&#x4E2D;&#x65AD;&#x3001;&#x809D;&#x7D30;&#x80DE;&#x306E;&#x8010;&#x6027;&#x8840;&#x6E05;&#x98E2;&#x9913;&#x3092;&#x524A;&#x6E1B;&#x3057;&#x307E;&#x3059;&#x3002;&#x4E00;&#x7DD2;&#x306B;&#x53D6;&#x3089;&#x308C;&#x3066;&#x3001;&#x79C1;&#x305F;&#x3061;&#x306E;&#x7814;&#x7A76;&#x306B;&#x304A;&#x3051;&#x308B; hmgb1 &#x306E;&#x767A;&#x73FE; BYSL &#x767A;&#x73FE;&#x306E;&#x809D;&#x767A;&#x764C;&#x304C;&#x5F79;&#x5272;&#x3092;&#x679C;&#x305F;&#x3059;&#x3053;&#x3068;&#x3092;&#x793A;&#x3057;&#x307E;&#x3059;&#x3002;

&#x30DE;&#x30FC;&#x30AF; Stin &#x69D8;&#x30BF;&#x30F3;&#x30D1;&#x30AF;&#x8CEA;&#x306B;&#x304A;&#x3051;&#x308B; hmgb1 &#x306E;&#x767A;&#x73FE;&#x809D;&#x7D30;&#x80DE;&#x764C;&#x3067;&#x3042;&#x308A; nucleologenesis &#x764C;&#x7D30;&#x80DE;&#x306E;&#x5897;&#x6B96;&#x306B;&#x5FC5;&#x8981;&#x306A;&#x3002;

&#xC774;&#xC804;&#xC5D0; bystin &#xAC19;&#xC740; (BYSL) &#xC720;&#xC804;&#xC790;&#xB294; &#xCD08;&#xAE30; &#xBC30;&#xC544; &#xC774;&#xC2DD;&#xC5D0; &#xCC38;&#xC5EC; &#xD558;&#xB294; &#xC138;&#xD3EC; &#xC811;&#xCC29;&#xC744; &#xC704;&#xD55C; &#xC561;&#xC138;&#xC11C;&#xB9AC; &#xB2E8;&#xBC31;&#xC9C8;&#xC744; &#xD2B9;&#xC9D5;&#xC785;&#xB2C8;&#xB2E4;. &#xB610;&#xD55C; 40 &#xB300; ribosomal &#xC18C; &#xB2E8;&#xC704; &#xC18D;&#xC5D0; &#xCC38;&#xC5EC; &#xD558; &#xACE0; &#xBE60;&#xB974;&#xAC8C; &#xC131;&#xC7A5; &#xD558;&#xB294; &#xD0DC;&#xC544; &#xBC0F; &#xC554; &#xC138;&#xD3EC; &#xB77C;&#xC778;&#xC5D0; &#xD45C;&#xD604;&#xD560; &#xC218; &#xC788;&#xC2B5;&#xB2C8;&#xB2E4;. &#xC554; &#xC138;&#xD3EC; &#xC99D;&#xC2DD; &#xBC0F; &#xC131;&#xC7A5;&#xC5D0; BYSL&#xC758; &#xC5ED;&#xD560;&#xC744; &#xD0D0;&#xAD6C; &#xD558;&#xAE30; &#xC704;&#xD574; &#xBAA8;&#xB378;&#xB85C; &#xAC04;&#xC138;&#xD3EC; &#xC554; (HCC)&#xB97C; &#xC0AC;&#xC6A9; &#xD588;&#xC2B5;&#xB2C8;&#xB2E4;. &#xC5EC;&#xAE30;&#xC5D0;&#xC11C;, &#xC6B0;&#xB9AC;&#xB294; BYSL HCC &#xC138;&#xD3EC;&#xC758; &#xC0DD;&#xCCB4; &#xC678; &#xBC0F; &#xC0DD;&#xCCB4; &#xC870;&#xAC74; &#xC131;&#xC7A5;&#xC744; &#xC704;&#xD574; &#xC911;&#xC694; &#xD558;&#xB2E4;&#xB294; &#xBCF4;&#xACE0; &#xD569;&#xB2C8;&#xB2E4;. &#xC2DD; &#xC218;&#xC900;&#xC758; BYSL Mrna&#xC640; &#xB2E8;&#xBC31;&#xC9C8;&#xC774; &#xC778;&#xAC04;&#xC758; HCC &#xD45C;&#xBCF8;&#xC740; &#xC778;&#xC811; &#xD55C; &#xBE44; &#xC554; &#xC870;&#xC9C1;&#xC5D0;&#xC11C; &#xBCF8; &#xADF8; &#xBE44;&#xD574; &#xD604;&#xC800; &#xD558; &#xAC8C; &#xC99D;&#xAC00; &#xD588;&#xB2E4;. &#xCCB4; &#xC678;, &#xC9E7;&#xC740; &#xD5E4;&#xC5B4;&#xD540; RNA&#xC5D0; &#xC758;&#xD574; BYSL&#xC758; &#xC800;&#xD574; HCC &#xC138;&#xD3EC; &#xC99D;&#xC2DD; &#xAC10;&#xC18C;, apoptosis &#xC720;&#xB3C4; &#xBC0F; &#xBD80;&#xBD84;&#xC801;&#xC73C;&#xB85C; &#xC138;&#xD3EC; &#xC8FC;&#xAE30;&#xC758; G2/M &#xB2E8;&#xACC4;&#xC5D0;&#xC11C; &#xCCB4;&#xD3EC;. Vivo&#xC5D0;&#xC11C; HCC &#xC140; BYSL Sirna&#xB85C; &#xCE58;&#xB8CC; &#xC2E4;&#xD328; &#xB204;&#xB4DC; &#xB9C8;&#xC6B0;&#xC2A4;&#xC5D0;&#xC11C; &#xC885;&#xC591; &#xD615;&#xD0DC;&#xB97C; &#xD53C;&#xD558; &#xC8FC;&#xC785; &#xD6C4;. BYSL RNAi &#xC720;&#xB3C4; &#xC138;&#xD3EC; &#xC131;&#xC7A5; &#xCCB4;&#xD3EC;, BYSL subcellular &#xC9C0;&#xC5ED;&#xD654; mitotic &#xC140;&#xB8F0;&#xB7EC; &#xAE30;&#xC900; &#xD655;&#xC778; &#xBC0F; HepG2 &#xC138;&#xD3EC; interphase &#xC870;&#xC0AC; &#xB418;&#xC5C8;&#xB2E4;. BYSL nucleologenesis, &#xC720;&#xC0AC; &#xBD84;&#xC5F4; &#xC911; &#xD575;&#xC18C;&#xCCB4; &#xD30C;&#xC0DD; foci (NDF), perichromosomal &#xC9C0;&#xC5ED; &#xBC0F; prenucleolar &#xBCF8;&#xBB38; (PNB) &#xD3EC;&#xD568; &#xD558;&#xB294; &#xB3D9;&#xC548; &#xC5EC;&#xB7EC; &#xB2E8;&#xACC4;&#xC5D0;&#xC11C; &#xC81C;&#xC2DC; &#xD588;&#xB2E4;. BYSL &#xACE0;&#xAC08; &#xD604;&#xC800; &#xD558; &#xAC8C; NDF &#xBC0F; PNB &#xD615;&#xC131; &#xC5B5;&#xC81C; &#xBC0F; &#xC99D;&#xAC00; apoptosis&#xC758; &#xACB0;&#xACFC;&#xB85C; &#xC720;&#xC0AC; &#xBD84;&#xC5F4;, &#xD6C4; nucleoli &#xC5B4;&#xC148;&#xBE14;&#xB9AC; &#xC911;&#xB2E8; &#xBC0F; &#xD608; &#xCCAD; &#xAE30;&#xC544; &#xD558; HCC &#xC140;&#xC758; &#xD5C8;&#xC6A9; &#xC624;&#xCC28;&#xB97C; &#xAC10;&#xC18C;. &#xD568;&#xAED8; &#xCC0D;&#xC740;, &#xC6B0;&#xB9AC;&#xC758; &#xC5F0;&#xAD6C; &#xB098;&#xD0C0;&#xB0C5;&#xB2C8;&#xB2E4; upregulated BYSL &#xC2DD; hepatocarcinogenesis&#xC5D0;&#xC11C; &#xD55C; &#xC5ED;&#xD560;&#xC744; &#xD55C;&#xB2E4;.

Bystin &#xAC19;&#xC740; &#xB2E8;&#xBC31;&#xC9C8;&#xACFC; &#xAC04;&#xC138;&#xD3EC; &#xC554; &#xC885;&#xC5D0;&#xC11C; upregulated&#xC740; nucleologenesis&#xC5D0;&#xC11C; &#xC554; &#xC138;&#xD3EC; &#xC99D;&#xC2DD;&#xC5D0; &#xD544;&#xC694;&#xD55C;.

El gen (BYSL) de bystin-como se caracteriz&oacute; anteriormente para codificar una prote&iacute;na accesoria de adhesi&oacute;n celular que participa en la implantaci&oacute;n del embri&oacute;n temprano. Tambi&eacute;n participa en la biog&eacute;nesis de subunidad ribosomal 40S y se encuentra a expresarse en l&iacute;neas celulares de embri&oacute;n y c&aacute;ncer de r&aacute;pido crecimiento. Para explorar el papel de BYSL en el crecimiento y proliferaci&oacute;n de c&eacute;lulas de c&aacute;ncer, utilizamos el carcinoma hepatocelular (HCC) como un modelo. Aqu&iacute;, Divulgamos que BYSL es crucial para el crecimiento de c&eacute;lulas HCC tanto in vitro como in vivo. Niveles de expresi&oacute;n de mRNA BYSL y prote&iacute;na en espec&iacute;menes humanos de HCC fueron aumentados marcado en comparaci&oacute;n con los de tejido no canceroso adyacente. In vitro, inhibici&oacute;n de la BYSL por short hairpin RNA disminuye la proliferaci&oacute;n de c&eacute;lulas HCC, indujo apoptosis y hab&iacute;a detenido parcialmente el ciclo celular en la fase G2/M. In vivo, c&eacute;lulas HCC tratadas con BYSL siRNA fallaron a los tumores en ratones desnudos forma despu&eacute;s de la implantaci&oacute;n subcut&aacute;nea. Para determinar las bases celulares para la detenci&oacute;n de crecimiento celular inducida por ARNi BYSL, localizaci&oacute;n subcelular BYSL en mitosis e interfase c&eacute;lulas HepG2 fue examinado. BYSL estuvo presente en varias etapas durante nucleologenesis, incluyendo en focos derivado del nucleolo (FDN), regiones de perichromosomal y el cuerpo prenucleolar (PNB) durante la mitosis. Agotamiento BYSL notable suprime la formaci&oacute;n de FDN y PNB y hab&iacute;a perturbado Asamblea nucleolos despu&eacute;s de la mitosis, dando por resultado mayor apoptosis y reduce la tolerancia de las c&eacute;lulas HCC al hambre de suero. Tomados en conjunto, nuestros estudios indican que la expresi&oacute;n de BYSL upregulated desempe&ntilde;a un papel en hepatocarcinogenesis.

Bystin-como la prote&iacute;na es el alza en el carcinoma hepatocelular y necesaria para nucleologenesis en la proliferaci&oacute;n de c&eacute;lulas de c&aacute;ncer.

MicroRNAs (miRNAs) modulate complex physiological and pathological processes by repressing expression of multiple components of cellular regulatory networks. Here we demonstrate that miRNAs encoded by the miR-23∼27∼24 gene clusters are enriched in endothelial cells and highly vascularized tissues. Inhibition of miR-23 and miR-27 function by locked nucleic acid-modified anti-miRNAs represses angiogenesis in vitro and postnatal retinal vascular development in vivo. Moreover, miR-23 and miR-27 are required for pathological angiogenesis in a laser-induced choroidal neovascularization mouse model. MiR-23 and miR-27 enhance angiogenesis by promoting angiogenic signaling through targeting Sprouty2 and Sema6A proteins, which exert antiangiogenic activity. Manipulating miR-23/27 levels may have important therapeutic implications in neovascular age-related macular degeneration and other vascular disorders.

Regulation of angiogenesis and choroidal neovascularization by members of microRNA-23~27~24 clusters.

Since their recent discovery, miRNAs have been shown to play critical roles in a variety of pathophysiological processes. Such processes include pathological angiogenesis, the oxidative stress response, immune response and inflammation, all of which have been shown to have important and interdependent roles in the pathogenesis and progression of age-related macular degeneration (AMD). Here we present a brief review of the pathological processes involved in AMD and review miRNAs and other noncoding RNAs involved in regulating these processes. Specifically, we discuss several candidate miRNAs that show promise as AMD therapeutic targets due to their direct involvement in choroidal neovascularization or retinal pigment epithelium atrophy. We discuss potential miRNA-based therapeutics and delivery methods for AMD and provide future directions for the field of miRNA research with respect to AMD. We believe the future of miRNAs in AMD therapy is promising.

miRNAs as potential therapeutic targets for age-related macular degeneration.

Primitive erythropoiesis defines the onset of hematopoiesis in the yolk sac of the early embryo and is initiated by the emergence of progenitors assayed as colony-forming cells (EryP-CFCs). EryP-CFCs are detected for only a narrow window during embryonic development, suggesting that both their initiation and termination are tightly controlled. Using the embryonic stem differentiation system to model primitive erythropoiesis, we found that miR-126 regulates the termination of EryP-CFC development. Analyses of miR-126 null embryos revealed that this miR also regulates EryP-CFCs in vivo. We identified vascular cell adhesion molecule-1 (Vcam-1) expressed by a mesenchymal cell population as a relevant target of miR-126. Interaction of EryP-CFCs with Vcam-1 accelerated their maturation to ßh1-globin(+) and Ter119(+) cells through a Src family kinase. These findings uncover a cell nonautonomous regulatory pathway for primitive erythropoiesis that may provide insight into the mechanism(s) controlling the developmental switch from primitive to definitive hematopoiesis.

Primitive erythropoiesis is regulated by miR-126 via nonhematopoietic Vcam-1+ cells.

Neovascularization (NV) in the cornea is a major cause of vision impairment and corneal blindness. Hemangiogenesis and lymphangiogenesis induced by inflammation underlie the pathogenesis of corneal NV. The current mainstay treatment, corticosteroid, treats the inflammation associated with corneal NV, but is not satisfactory due to such side effects as cataract and the increase in intraocular pressure. It is imperative to develop a novel therapy that specifically targets the hemangiogenesis, lymphangiogenesis, and inflammation pathways underlying corneal NV. Histone deacetylase inhibitors (HDACi) have been in clinical trials for cancer and other diseases. In particular, HDACi suberoylanilide hydroxamic acid (SAHA, vorinostat, Zolinza) has been approved by the FDA for the treatment of cutaneous T-cell lymphoma. The functional mechanism of SAHA in cancer and especially in corneal NV remains unclear. Here, we show that topical application of SAHA inhibits neovascularization in an alkali-burn corneal injury model. Mechanistically, SAHA inhibits corneal NV by repressing hemangiogenesis, inflammation pathways, and previously overlooked lymphangiogenesis. Topical SAHA is well tolerated on the ocular surface. In addition, the potency of SAHA in corneal NV appears to be comparable to the current steroid therapy. SAHA may possess promising therapeutic potential in alkali-burn corneal injury and other inflammatory neovascularization disorders.

Inhibition of multiple pathogenic pathways by histone deacetylase inhibitor SAHA in a corneal alkali-burn injury model.

Actin cytoskeleton is critical for cell motility and division, both of which are important for angiogenesis. MicroRNAs (miRNA/miR) are emerging as pivotal modulators of vascular development and disease. How miRNAs regulate actin cytoskeleton dynamics in endothelial cells (EC) and neovascularization is still unclear. Here, we report that miR-24 regulates actin dynamics in ECs through targeting multiple members downstream of Rho signaling, including Pak4, Limk2, and Diaph1 proteins. Overexpression of miR-24 in ECs blocks stress fiber and lamellipodia formation, represses EC migration, proliferation, and tube formation in vitro, as well as angiogenesis in an ex vivo aortic ring assay. Moreover, subretinal delivery of miR-24 mimics represses laser-induced choroidal neovascularization (CNV) in vivo. Mechanistically, knockdown of miR-24 target protein LIMK2 or PAK4 inhibits stress fiber formation and tube formation in vitro, mimicking miR-24 overexpression phenotype in angiogenesis, while overexpression of LIMK2 and PAK4 by adenoviruses partially rescued the tube formation defects in miR-24 overexpressing ECs. Taken together, these findings suggest that miR-24 represses angiogenesis by simultaneously regulating multiple components in the actin cytoskeleton pathways. Manipulation of actin cytoskeleton pathways by miR-24 may represent an attractive therapeutic solution for the treatment of wet age-related macular degeneration (AMD) and other vascular diseases.

Qinbo Zhou

Department of Cell and Molecular Biology

Tulane University

An Alkali-burn Injury Model of Corneal Neovascularization in the Mouse

Qinbo Zhou

.css-o250i3{font-size:18px;font-family:Open Sans,sans-serif;line-height:21.6px;}Department of Cell and Molecular Biology

Tulane University

An Alkali-burn Injury Model of Corneal Neovascularization in the Mouse

Department of Cell and Molecular Biology