Apolipoprotein L1 Dynamics in Human Parietal Epithelial Cell Molecular Phenotype Kinetics

Kumar, V.; Vashistha, H.; Lan, X.; Chandel, N.; Ayasolla, K.; Aslam, R.; Marshi Shoshtari, S. S.; Paliwal, N.; Abbruscato, F.; Mikulak, J.; Popik, W.; Malhotra, A.; Meyer-Scwesinger, C.; Skorecki, K.; Singhal, P. C.

doi:10.1101/259267

bioRxiv · 10.1101/259267

Apolipoprotein L1 Dynamics in Human Parietal Epithelial Cell Molecular Phenotype Kinetics

Kumar, V.·Vashistha, H.·Lan, X.·Chandel, N.·Ayasolla, K.·Aslam, R.·Marshi Shoshtari, S. S.·Paliwal, N.·Abbruscato, F.·Mikulak, J.·Popik, W.·Malhotra, A.·Meyer-Scwesinger, C.·Skorecki, K.·Singhal, P. C.

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Abstract

Human Parietal Epithelial cells (PECs) are considered as a source of progenitor cells to sustain podocyte (PD) homeostasis. We hypothesized that the absence of apolipoprotein (APO) L1 favors the PEC phenotype and that induction of APOL1 transitions to PD renewal. During PECs transition, APOL1 expression coincided with the expression of PD markers (PEC transition) along with down regulation of miR193a. The induction of APOL1 down regulated miR193a and induced PD markers in PECs/HEKs; whereas, the APOL1-silencing in transited (Tr)-PECs/HepG2s up regulated miR193a expression suggesting a reciprocally linked feedback loop relationship between APOL1 and miR193a. HIV, IFN-y, and vitamin D receptor agonist (VDA) induced APOL1 expression and PEC transition markers but down regulated miR193a in PECs/HEKs. Glomeruli in HIV patients and HIV: APOL1 transgenic mice displayed foci of PECs expressing synaptopodin, a PEC transition marker. Since APOL1 silencing in PECs partially attenuated HIV-, VDA-, and IFN-y-induced PECs transition, this would suggest that APOL1 is an important functional constituent of APOL1-miR193a axis.

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Kumar, V., Vashistha, H., Lan, X., Chandel, N., Ayasolla, K., Aslam, R., Marshi Shoshtari, S. S., Paliwal, N., Abbruscato, F., Mikulak, J., Popik, W., Malhotra, A., Meyer-Scwesinger, C., Skorecki, K., Singhal, P. C.. 2018-02-04. Apolipoprotein L1 Dynamics in Human Parietal Epithelial Cell Molecular Phenotype Kinetics. https://doi.org/10.1101/259267

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