title: Rapamycin-induced modulation of miRNA expression is associated with amelioration of HIV-associated nephropathy (HIVAN).
abstract: Recent studies suggested that miRNAs are involved in the development of the pathogenesis of HIV-associated nephropathy (HIVAN). Rapamycin, a widely used mTOR inhibitor, has been demonstrated to slow down the progression of HIVAN. However, the role of miRNA in the regulation of these processes has not been investigated so far. In the current study, we have used a microarray-based approach in combination with real-time PCR to profile the miRNA expression patterns in rapamycin-treated HIVAN mice (Tg26). Our results demonstrated that 19 miRNAs belonging to 13 different families expressed differentially in renal tissues of rapamycin-receiving Tg26 mice when compared to Tg26 mice-receiving saline only. The patterns of miRNAs expression in rapamycin-receiving Tg26 mice took a reverse turn. These miRNAs were classified into 8 functional categories. In in vitro studies, we examined the expression of specific miRNAs in HIV-1 transduced human podocytes (HIV/HPs). HIV/HPs displayed attenuation of expression of miR-99a, -100a, -199a and miR-200, whereas, rapamycin inhibited this effect of HIV. These findings suggest that rapamycin-mediated up-regulation of specific miRNAs could contribute to amelioration of renal lesions in HIVAN mice.
authors.affiliation: Department of Medicine, Hofstra North Shore LIJ Medical School and Feinstein Institute for Medical Research, NY, United States.
authors.forename: Kang
authors.initials: K
authors.lastname: Cheng
authors.affiliation: Department of Medicine, Hofstra North Shore LIJ Medical School and Feinstein Institute for Medical Research, NY, United States.
authors.forename: Partab
authors.initials: P
authors.lastname: Rai
authors.affiliation: Department of Medicine, Hofstra North Shore LIJ Medical School and Feinstein Institute for Medical Research, NY, United States.
authors.forename: Andrei
authors.initials: A
authors.lastname: Plagov
authors.affiliation: Department of Medicine, Hofstra North Shore LIJ Medical School and Feinstein Institute for Medical Research, NY, United States.
authors.forename: Xiqian
authors.initials: X
authors.lastname: Lan
authors.affiliation: Department of Medicine, Hofstra North Shore LIJ Medical School and Feinstein Institute for Medical Research, NY, United States.
authors.forename: Peter W
authors.initials: PW
authors.lastname: Mathieson
authors.affiliation: Department of Medicine, Hofstra North Shore LIJ Medical School and Feinstein Institute for Medical Research, NY, United States.
authors.forename: Moin A
authors.initials: MA
authors.lastname: Saleem
authors.affiliation: Department of Medicine, Hofstra North Shore LIJ Medical School and Feinstein Institute for Medical Research, NY, United States.
authors.forename: Mohammad
authors.initials: M
authors.lastname: Husain
authors.affiliation: Department of Medicine, Hofstra North Shore LIJ Medical School and Feinstein Institute for Medical Research, NY, United States.
authors.forename: Ashwani
authors.initials: A
authors.lastname: Malhotra
authors.affiliation: Department of Medicine, Hofstra North Shore LIJ Medical School and Feinstein Institute for Medical Research, NY, United States. Electronic address: psinghal@nshs.edu.
authors.forename: Pravin C
authors.initials: PC
authors.lastname: Singhal
mesh_terms: D016263:AIDS-Associated Nephropathy / Q000235:genetics* / Q000473:pathology / Q000517:prevention & control; D000818:Animals; D002478:Cells, Cultured; D018450:Disease Progression; D004353:Drug Evaluation, Preclinical; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D015497:HIV-1 / Q000502:physiology; D006367:HeLa Cells; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D035683:MicroRNAs / Q000235:genetics*; D020123:Sirolimus / Q000494:pharmacology*
chemical_list: D007166:Immunosuppressive Agents; D035683:MicroRNAs; D020123:Sirolimus
keywords: Apoptosis; Epithelial mesanchymal transition; HIV-associated nephropathy; Mammalian target of rapamycin; MicroRNA