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Role of mTOR signaling in compensatory hypertrophy following uninephrectomy in the rat
Author(s) -
Myung Choi,
Oyekan Adebayo
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.27.1_supplement.703.5
Subject(s) - medicine , endocrinology , pi3k/akt/mtor pathway , kidney , protein kinase b , muscle hypertrophy , chemistry , signal transduction , biology , biochemistry
Loss of functional nephrons following kidney injury or uninephrectomy (UNx) often results in functional and structural changes in the kidney such as compensatory hypertrophy. The eNOS/NO pathway has been shown to play a critical role in compensatory renal growth by modulating hemodynamic changes. As NO stimulates the Akt‐mTOR (mammalian target of rapamycin) pathway via the sGC/PKG pathway, this study tested the hypothesis that mTOR is a downstream signaling pathway in compensatory renal hypertrophy. In rats subjected to sham or UNx in the presence or absence of methylene blue (MB), an inhibitor of sGC, with or without rapamycin (Rapa), an inhibitor of mTOR, UNx induced an increase in kidney/body weight ratio (P<0.05) that was not affected by MB or Rapa. However, renal tissue DNA was increased following UNx (34%; P<0.05). MB further increased this (85%; P<0.01) while Rapa abolished the MB effect. Similarly, pAkt expression was increased by UNx (P<0.05) and blunted by MB (P<0.05). These changes were accompanied by UNx‐induced nitrite excretion (U NOx V; P<0.05) which was blunted by MB (P<0.05). Rapa blunted the MB effect (P<0.05). Blood pressure was unchanged by UNx, MB, or Rapa. Proteinuria (U Prot V) was also not affected by UNx but MB increased U Prot V (P<0.05) and Rapa paradoxically exarcerbated it (P<0.05). Despite this, serum creatinine (S Cr ) was unchanged in all the groups. However, UNx increased sodium excretion (U Na V; P<0.05) but was unaffected by MB or Rapa. We conclude that the Akt‐MTOR signaling pathway is involved in renal growth and is linked to renal NO production.