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An Efficient and Fast Method for Labeling and Analyzing Mouse Glomeruli

The glomeruli are fundamental units in the kidney; hence, studying the glomeruli is pivotal for understanding renal function and pathology. Biological ...

Sichuan University

Pressure overload causes an accumulation of homocysteine in the heart, which is accompanied by copper depletion through the formation of copper-homocysteine complexes and the excretion of the complexes. Copper supplementation recovers cytochrome c oxidase (CCO) activity and promotes myocardial angiogenesis, along with the regression of cardiac hypertrophy and the recovery of cardiac contractile function. Increased copper availability is responsible for the recovery of CCO activity. Copper promoted expression of angiogenesis factors including vascular endothelial growth factor (VEGF) in endothelial cells is responsible for angiogenesis. VEGF receptor-2 (VEGFR-2) is critical for hypertrophic growth of cardiomyocytes and VEGFR-1 is essential for the regression of cardiomyocyte hypertrophy. Copper, through promoting VEGF production and suppressing VEGFR-2, switches the VEGF signaling pathway from VEGFR-2-dependent to VEGFR-1-dependent, leading to the regression of cardiomyocyte hypertrophy. Copper is also required for hypoxia-inducible factor-1 (HIF-1) transcriptional activity, acting on the interaction between HIF-1 and the hypoxia responsible element and the formation of HIF-1 transcriptional complex by inhibiting the factor inhibiting HIF-1. Therefore, therapeutic targets for copper supplementation-induced regression of cardiac hypertrophy include: (1) the recovery of copper availability for CCO and other critical cellular events; (2) the activation of HIF-1 transcriptional complex leading to the promotion of angiogenesis in the endothelial cells by VEGF and other factors; (3) the activation of VEGFR-1-dependent regression signaling pathway in the cardiomyocytes; and (4) the inhibition of VEGFR-2 through post-translational regulation in the hypertrophic cardiomyocytes. Future studies should focus on target-specific delivery of copper for the development of clinical application.

Role of copper in regression of cardiac hypertrophy.

The word "rejuvenate" found in the Merriam-Webster dictionary is (1) to make young or youthful again: give new vigor to, and (2) to restore to an original or new state. Regenerative medicine is the process of creating living, functional tissues to repair or replace tissue or organ function lost due to age, disease, damage, or congenital defects. To accomplish this, approaches including transplantation, tissue engineering, cell therapy, and gene therapy are brought into action. These all use exogenously prepared materials to forcefully mend the failed organ. The adaptation of the materials in the host and their integration into the organ are all uncertain. It is a common sense that tissue injury in the younger is easily repaired and the acute injury is healed better and faster. Why does the elder have a diminished capacity of self-repairing, or why does chronic injury cause the loss of the self-repairing capacity? There must be some critical elements that are involved in the repair process, but are suppressed in the elder or under the chronic injury condition. Rejuvenation of the self-repair mechanism would be an ideal solution for functional recovery of the failed organ. To achieve this, it would involve renewal of the injury signaling, reestablishment of the communication and transportation system, recruitment of the materials for repairing, regeneration of the failed organ, and rehabilitation of the renewed organ. It thus would require a comprehensive understanding of developmental biology and a development of new approaches to activate the critical players to rejuvenate the self-repair mechanism in the elder or under chronic injury condition. Efforts focusing on rejuvenation would expect an alternative, if not a better, accomplishment in the regenerative medicine.

Rejuvenation: an integrated approach to regenerative medicine.

Endothelial progenitor cells (EPCs) are increasingly becoming a major focus of regenerative medicine research and practice. The present study was undertaken to establish an appropriate procedure for isolation and characterization of EPCs from Rhesus monkeys for regenerative medicine research.

Isolation and characterization of endothelial progenitor cells from Rhesus monkeys.

Vascular network labeling in transparent tissues provides more complete information on blood vessels. To achieve a fast and efficient method for vascular network labeling in transparent tissues, we compared various vascular labeling methods under different tissue clearing protocols. FITC-Dextran labeling and CUBIC cleaning treatment were found to be the best options for vascular network labeling in cleared mouse tissues. Satisfactory labeling of vascular networks in various organs can be achieved by selecting FITC-Dextran with different molecular weights and different administration methods.

Lily Zheng

Regenerative Medicine Research Center,
West China Hospital,
Regenerative Medicine Research Center, West China Hospital

Sichuan University

An Efficient and Fast Method for Labeling and Analyzing Mouse Glomeruli

Lily Zheng

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Sichuan University

An Efficient and Fast Method for Labeling and Analyzing Mouse Glomeruli

Regenerative Medicine Research Center,
West China Hospital,
Regenerative Medicine Research Center, West China Hospital