Document Detail


Sirolimus modulates HIVAN phenotype through inhibition of epithelial mesenchymal transition.
MedLine Citation:
PMID:  22579465     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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 expression (a repressor of E-cadherin transcription), it appears that sirolimus may be attenuating renal cell EMT by preserving epithelial cell E-cadherin expression.
Authors:
Anju Yadav; Dileep Kumar; Divya Salhan; Rungwasee Rattanavich; Subani Maheshwari; Madhuri Adabala; Guohua Ding; Pravin C Singhal
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2012-05-02
Journal Detail:
Title:  Experimental and molecular pathology     Volume:  93     ISSN:  1096-0945     ISO Abbreviation:  Exp. Mol. Pathol.     Publication Date:  2012 Aug 
Date Detail:
Created Date:  2012-06-11     Completed Date:  2012-08-24     Revised Date:  2013-08-14    
Medline Journal Info:
Nlm Unique ID:  0370711     Medline TA:  Exp Mol Pathol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  173-81     Citation Subset:  IM    
Copyright Information:
Copyright © 2012 Elsevier Inc. All rights reserved.
Affiliation:
Immunology Center, Feinstein Institute for Medical Research, North Shore-Long Island Jewish Health System, Manhasset, NY 11030, United States.
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MeSH Terms
Descriptor/Qualifier:
AIDS-Associated Nephropathy / drug therapy*,  metabolism,  pathology
Actins / analysis
Animals
Anti-HIV Agents / therapeutic use*
Cadherins / biosynthesis
Calcium-Binding Proteins / analysis
Cell Proliferation / drug effects*
Disease Models, Animal
Epithelial-Mesenchymal Transition / drug effects*
Female
Homeodomain Proteins / analysis
Humans
Immunohistochemistry
Kidney Glomerulus / drug effects,  metabolism,  pathology
Kidney Tubules / drug effects,  metabolism,  pathology
Male
Mice
Mice, Transgenic
Sirolimus / therapeutic use*
Transcription Factors / analysis
Vimentin / analysis
Grant Support
ID/Acronym/Agency:
R01 DK083931/DK/NIDDK NIH HHS; R01 DK083931/DK/NIDDK NIH HHS; R01 DK084910/DK/NIDDK NIH HHS; R01DK084910/DK/NIDDK NIH HHS
Chemical
Reg. No./Substance:
0/ACTA2 protein, human; 0/Actins; 0/Anti-HIV Agents; 0/Cadherins; 0/Calcium-Binding Proteins; 0/FSP1 protein, human; 0/Homeodomain Proteins; 0/Transcription Factors; 0/Vimentin; 0/ZEB1 protein, human; 53123-88-9/Sirolimus
Comments/Corrections

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