Role of Apolipoprotein L1 in Human Parietal Epithelial Cell Transition
Human parietal epithelial cells (PECs) are progenitor cells that sustain podocyte homeostasis. We hypothesized that the lack of apolipoprotein (APO) L1 ensures the PEC phenotype, but its induction initiates PEC transition (expression of podocyte markers). APOL1 expression and down-regulation of miR193a coincided with the expression of podocyte markers during the transition. The induction of APOL1 also stimulated transition markers in human embryonic kidney cells (cells with undetectable APOL1 protein expression). APOL1 silencing in PECs up-regulated miR193a expression, suggesting the possibility of a reciprocal feedback relationship between APOL1 and miR193a. HIV, interferon-gamma, and vitamin D receptor agonist down-regulated miR193a expression and induced APOL1 expression along with transition markers in PECs. Luciferase assay suggested a putative interaction between miR193a and APOL1. Since silencing of APOL1 attenuated HIV-, vitamin D receptor agonist-, miR193a inhibitor-, and interferon-gamma-induced expression of transition markers, APOL1 appears to be a critical functional constituent of the miR193a- APOL1 axis in PECs. This notion was confirmed by further enhanced expression of PEC markers in APOL1 mRNA-silenced PECs. In vivo studies, glomeruli in patients with HIV, and HIV/APOL1 transgenic mice had foci of PECs expressing synaptopodin, a transition marker. APOL1 likely regulates PEC molecular phenotype through modulation of miR193a expression, and APOL1 and miR193a share a reciprocal feedback relationship.
Kumar, V., Vashistha, H., Lan, X., Chandel, N., Ayasolla, K., Shoshtari, S., Aslam, R., Paliwal, N., Abbruscato, F., Mikulak, J., Popik, W., Atta, M., Chander, P., Malhotra, A., Meyer-Schwesinger, C., Skorecki, K., & Singhal, P. (2018). Role of Apolipoprotein L1 in Human Parietal Epithelial Cell Transition. American Journal of Pathology, 188 (11), 2508-2528. https://doi.org/10.1016/j.ajpath.2018.07.025