The functionality of oUSCs in the context of antiretroviral agents such as TFV (IMAGE)
Caption
Upon entering USC, TFV induces a significant reduction in telomere parameters (TRF1 and telomerase activity proteins), which subsequently leads to a reduction in PGC1-α expression. This reduction in PGC1-α initiates mitochondrial dysfunction characterized by decreased mtTFA protein expression, increased SOD2 expression, decreased mtDNA content, and disruption of ETC complexes I–V. These changes result in a decrease in USC telomerase activity, indicating a loss of stem cell properties, and an increase in aging-related genes and markers, including β-Gal. In addition, increased levels of KIM-1 protein, CYP2E1, and cleaved-caspase3/caspase3 indicate cellular injury, reduced drug metabolism capacity, and the initiation of apoptosis in renal progenitor cells. Notably, the effect of TFV on oUSCs is exacerbated by their telomere-mitochondrial dysfunction compared with yUSCs.
Credit
Pengfei Yu, Huifen Ding, Jian-Xing Ma, Zhongping Duan, Yu Chen, Anthony Atala, Yuanyuan Zhang
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CC BY-NC-ND