Renin angiotensin system modulates mTOR pathway through AT2R in HIVAN

Partab Rai, Rivka Lederman, Shabirul Haque, Shabina Rehman, Viki Kumar, Kavithalakshmi Sataranatrajan, Ashwani Malhotra, Balakuntalam S. Kasinath, Pravin C. Singhal

Research output: Contribution to journalArticlepeer-review

4 Scopus citations

Abstract

Mammalian target of rapamycin (mTOR) has been reported to contribute to the development of HIV-associated nephropathy (HIVAN). We hypothesized that HIV may be activating renal tissue mTOR pathway through renin angiotensin system (RAS) via Angiotensin Receptor Type II receptor (AT2R). Renal tissues of Vpr transgenic and Tg26 (HIVAN) mice displayed enhanced phosphorylation of mTOR and p70S6K. Aliskiren, a renin inhibitor attenuated phosphorylation of both mTOR and p70S6K in renal tissues of HIVAN mice. Interestingly, Angiotensin Receptor Type I (AT1R) blockade did not modulate renal tissue phosphorylation of mTOR in HIVAN mice; on the other hand, AT2R blockade attenuated renal tissue phosphorylation of mTOR in HIVAN mice. In vitro studies, both renin and Ang II displayed enhanced mouse tubular cell (MTC) phosphorylation of p70S6K in a dose dependent manner. HIV/MTC also displayed enhanced phosphorylation of both mTOR and p70S6K; interestingly this effect of HIV was further enhanced by losartan (an AT1R blocker). On the other hand, AT2R blockade attenuated HIV-induced tubular cell phosphorylation of mTOR and p70S6K, whereas, AT2R agonist enhanced phosphorylation of mTOR and p70S6K. These findings indicate that HIV stimulates mTOR pathway in HIVAN through the activation of renin angiotensin system via AT2R.

Original languageEnglish (US)
Pages (from-to)431-437
Number of pages7
JournalExperimental and Molecular Pathology
Volume96
Issue number3
DOIs
StatePublished - Jun 2014

Keywords

  • Angiotensin II type 1 receptor
  • Angiotensin II type II receptor
  • Renal proximal tubular cells
  • Renin

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Molecular Biology
  • Clinical Biochemistry

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