Sirolimus modulates HIVAN phenotype through inhibition of epithelial mesenchymal transition.

Experimental and Molecular Pathology
Anju YadavPravin C Singhal

Abstract

HIV-associated nephropathy (HIVAN) is characterized by proliferative phenotype in the form of collapsing glomerulopathy and microcystic dilatation of tubules. Recently, epithelial mesenchymal transition (EMT) of renal cells has been demonstrated to contribute to the pathogenesis of proliferative HIVAN phenotype. We hypothesized that sirolimus would modulate HIVAN phenotype by attenuating renal cell EMT. In the present study, we evaluated the effect of sirolimus on the development of renal cell EMT as well as on display of HIVAN phenotype in a mouse model of HIVAN (Tg26). Tg26 mice receiving normal saline (TgNS) showed enhanced proliferation of both glomerular and tubular cells when compared to control mice-receiving normal saline (CNS); on the other hand, Tg26 mice receiving sirolimus (TgS) showed attenuated renal cell proliferation when compared with TgNS. TgNS also showed increased number of α-SMA-, vimentin-, and FSP1-positive cells (glomerular as well as tubular) when compared with CNS; however, TgS showed reduced number of SMA, vimentin, and FSP1+ve renal cells when compared to TgNS. Interestingly, sirolimus preserved renal epithelial cell expression of E-cadherin in TgS. Since sirolimus attenuated renal cell ZEB expressio...Continue Reading

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Citations

Sep 27, 2012·Experimental and Molecular Pathology·Partab RaiPravin C Singhal
Oct 23, 2012·Experimental and Molecular Pathology·Kang ChengPravin C Singhal
Feb 18, 2015·Nature Reviews. Nephrology·Avi Z RosenbergJeffrey B Kopp
Feb 15, 2017·Transplantation·Véronique Avettand-FenoëlGuillaume Canaud
Jun 23, 2018·Frontiers in Medicine·Samuel J Rednor, Michael J Ross
Feb 6, 2017·Experimental Cell Research·Xiqian LanPravin C Singhal

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