Abstract: TH-PO947
Vitamin D Receptor Deficiency Promotes Premature Aging by Inducing Pericytes and Microvessel Loss
Session Information
- Geriatric Nephrology: Innovations and Insights
October 24, 2024 | Location: Exhibit Hall, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Geriatric Nephrology
- 1300 Geriatric Nephrology
Author
- Chen, Xujiao, Huashan Hospital Fudan University, Shanghai, Shanghai, China
Background
Aging is a complex process influenced by a variety of factors and demonstrates organ-specific characteristics. A common hallmark of pathological changes across various organs is the decline in microvascular density. However, the molecular mechanisms governing organ-specific microvascular decline and aging are still not well understood. Vitamin D receptor (VDR) plays a crucial role in maintaining vascular health, and its deficiency is associated with numerous age-related diseases. Nonetheless, whether VDR regulates the aging process via microvascular pathways remains unreported.
Methods
We extracted data in the Tabula Muris Senis database, and analyzed the changes in the expression of VDR with age. The VDR knockout mice was established and the changes of kidney, bone, heart, liver, lung, muscle, skin, spleen, and other tissues and organs at the age of 3 to 12 months in aging related indicators at the functional, histological and molecular biological levels were obeserved. Single cell RNA sequencing was performed in the kidneys of 6-month-old wild type and VDR knockout mice, while RNA velocity and pseudo-time analysis were used to simulate the dynamic changes of cell. adeno-associated virus (AAV) transfection technology was mainly used to carry out in vivo research in mice. Kidney pericyte-specific VDR knockdown and overexpress model were established to validate the function of pericyte in kidney aging. Finally, the effect of VDR on pericytes angiogenesis was investigated through 3D co-culture of pericytes and endothelial cells.
Results
In this study, we demonstrate that VDR deficiency leads to premature aging, prominently affecting the kidneys. Using single-cell RNA sequencing, we identified pericytes as the most significantly altered cell subtype within the kidney in VDR knockout mice. Further analysis revealed a marked decrease in pericytes and microvessels in both VDR knockout and kidney pericyte-specific VDR knockdown mice. Notably, an augmented pericyte-myofibroblast differentiation was observed, suggesting a potential mechanism underlying the observed microvascular dysfunction in the absence of VDR, which contributed to the aging process.
Conclusion
Our investigation into the role of VDR in the decline of pericytes and microvessels throughout the aging process holds the potential to unveil novel therapeutic strategies for delaying multi-organ aging.
Funding
- Government Support – Non-U.S.