Hypoxia induces ZEB2 in podocytes: Implications in the pathogenesis of proteinuria

Journal of Cellular Physiology
Krishnamurthy NakuluriAnil Kumar Pasupulati

Abstract

The glomerular filtration barrier (GFB) plays a critical role in ensuing protein free urine. The integrity of the GFB is compromised during hypoxia that prevails during extreme physiological conditions. However, the mechanism by which glomerular permselectivity is compromised during hypoxia remains enigmatic. Rats exposed to hypoxia showed a decreased glomerular filtration rate, podocyte foot-processes effacement, and proteinuria. Accumulation of hypoxia-inducible factor-1α (HIF1α) in podocytes resulted in elevated expression of zinc finger E-box binding homeobox 2 (ZEB2) and decreased expression of E- and P-cadherin. We also demonstrated that HIF1α binds to hypoxia response element localized in the ZEB2 promoter. Furthermore, HIF1α also induced the expression of ZEB2-natural antisense transcript, which is known to increase the efficiency of ZEB2 translation. Ectopic expression of ZEB2 induced loss of E- and P-cadherin and is associated with enhanced motility of podocytes during hypoxic conditions. ZEB2 knockdown abrogated hypoxia-induced decrease in podocyte permselectivity. This study suggests that hypoxia leads to activation of HIF1α-ZEB2 axis, resulting in podocyte injury and poor renal outcome.

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Citations

Jul 1, 2020·BMJ Open Diabetes Research & Care·Rajkishor NishadAnil Kumar Pasupulati
Sep 13, 2019·The Journal of Biological Chemistry·Rajkishor NishadAnil K Pasupulati
Feb 13, 2021·Cancers·Rania F ZaarourSalem Chouaib
Jan 6, 2021·Molecular Cancer·Xiaoxu WeiZhaoyang Zeng
Apr 3, 2021·Cell Death & Disease·Rajkishor NishadAnil K Pasupulati
Apr 4, 2021·Cancers·Leila JahangiriSuzanne D Turner
Apr 10, 2021·Journal of Physiology and Biochemistry·Ashish K SinghAnil K Pasupulati
Jun 1, 2021·Seminars in Cancer Biology·Hyun-Wook LeeSuresh Cuddapah

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