Role of mammalian target of rapamycin signaling in compensatory renal hypertrophy

Jiankang Chen, Jianchun Chen, Eric G. Neilson, Raymond C. Harris

Research output: Contribution to journalArticle

91 Citations (Scopus)

Abstract

Loss of functioning nephrons stimulates the growth of residual kidney tissue to augment work capacity and maintain normal renal function. This growth largely occurs by hypertrophy rather than from hyperplasia of the remaining nephrons. The signaling mechanisms that increase RNA and protein synthesis during compensatory renal hypertrophy are unknown. This study found that the remaining kidney hypertrophied 42% by 16 d after unilateral nephrectomy (UNX) in DBA/2 mice. Immunoblotting analysis revealed increased phosphorylation of the 40S ribosomal protein S6 (rpS6) and the eukaryotic translation initiation factor (eIF) 4E-binding protein 1 (4E-BP1), the two downstream effectors of the mammalian target of rapamycin (mTOR). The highly specific mTOR inhibitor rapamycin blocked UNX-increased phosphorylation of both rpS6 and 4E-BP1. UNX increased the content of not only 40S and 60S ribosomal subunits but also 80S monosomes and polysomes in the remaining kidney. Administration of rapamycin decreased UNX-induced polysome formation and shifted the polysome profile in the direction of monosomes and ribosomal subunits. Pretreatment of the mice with rapamycin inhibited UNX-induced hypertrophy. These studies demonstrate that activation of the mTOR signaling pathway in the remaining kidney after UNX plays an essential role in modulating RNA and protein synthesis during development of compensatory renal hypertrophy.

Original languageEnglish (US)
Pages (from-to)1384-1391
Number of pages8
JournalJournal of the American Society of Nephrology
Volume16
Issue number5
DOIs
StatePublished - Dec 9 2005
Externally publishedYes

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Sirolimus
Hypertrophy
Kidney
Polyribosomes
Ribosomal Protein S6
Nephrons
Carrier Proteins
Eukaryotic Large Ribosome Subunits
Eukaryotic Small Ribosome Subunits
Phosphorylation
Eukaryotic Initiation Factor-4E
RNA
Eukaryotic Initiation Factors
Ribosome Subunits
Inbred DBA Mouse
Growth
Nephrectomy
Immunoblotting
Hyperplasia
Proteins

ASJC Scopus subject areas

  • Nephrology

Cite this

Role of mammalian target of rapamycin signaling in compensatory renal hypertrophy. / Chen, Jiankang; Chen, Jianchun; Neilson, Eric G.; Harris, Raymond C.

In: Journal of the American Society of Nephrology, Vol. 16, No. 5, 09.12.2005, p. 1384-1391.

Research output: Contribution to journalArticle

Chen, Jiankang ; Chen, Jianchun ; Neilson, Eric G. ; Harris, Raymond C. / Role of mammalian target of rapamycin signaling in compensatory renal hypertrophy. In: Journal of the American Society of Nephrology. 2005 ; Vol. 16, No. 5. pp. 1384-1391.
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