Sirolimus modulates HIVAN phenotype through inhibition of epithelial mesenchymal transition.
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
References
The clinical epidemiology and course of the spectrum of renal diseases associated with HIV infection
Citations
Related Concepts
Related Feeds
Cadherins and Catenins
Cadherins (named for "calcium-dependent adhesion") are a type of cell adhesion molecule (CAM) that is important in the formation of adherens junctions to bind cells with each other. Catenins are a family of proteins found in complexes with cadherin cell adhesion molecules of animal cells: alpha-catenin can bind to β-catenin and can also bind actin. β-catenin binds the cytoplasmic domain of some cadherins. Discover the latest research on cadherins and catenins here.
Bioinformatics in Biomedicine
Bioinformatics in biomedicine incorporates computer science, biology, chemistry, medicine, mathematics and statistics. Discover the latest research on bioinformatics in biomedicine here.