HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: 297/3/F585    most recent 00186.2009v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Web of Science (1) Google Scholar Articles by Chen, J.-K. Articles by Harris, R. C. PubMed PubMed Citation Articles by Chen, J.-K. Articles by Harris, R. C.

EDITORIAL FOCUS

S6 kinase 1 knockout inhibits uninephrectomy- or diabetes-induced renal hypertrophy

¹Department of Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee, ²Department of Genome Science, Genome Research Institute, University of Cincinnati, Cincinnati, Ohio

Submitted 30 March 2009 ; accepted in final form 22 May 2009

Removal of one kidney stimulates synthesis of RNA and protein, with minimal DNA replication, in all nephron segments of the remaining kidney, resulting in cell growth (increase in cell size) with minimal cell proliferation (increase in cell number). In addition to the compensatory renal hypertrophy caused by nephron loss, pathophysiological renal hypertrophy can occur as a consequence of early uncontrolled diabetes. However, the molecular mechanism underlying renal hypertrophy in these conditions remains unclear. In the present study, we report that deletion of S6 kinase 1 (S6K1) inhibited renal hypertrophy seen following either contralateral nephrectomy or induction of diabetes. In wild-type mice, hypertrophic stimuli increased phosphorylation of 40S ribosomal protein S6 (rpS6), a known target of S6K1. Immunoblotting analysis revealed that S6K1^–/– mice exhibited moderately elevated basal levels of rpS6, which did not increase further in response to the hypertrophic stimuli. Northern blotting indicated a moderate upregulation of S6K2 expression in the kidneys of S6K1^–/– mice. Phosphorylation of the eukaryotic translation initiation factor 4E-binding protein 1, another downstream target of the mammalian target of rapamycin (mTOR), was stimulated to equivalent levels in S6K1^–/– and S6K1^+/+ littermates during renal hypertrophy, indicating that mTOR was still activated in the S6K1^–/– mice. The highly selective mTOR inhibitor, rapamycin, inhibited increased phosphorylation of rpS6 and blocked 60–70% of the hypertrophy seen in wild-type mice but failed to prevent the 10% hypertrophy seen in S6K1^–/– mice in response to uninephrectomy (UNX) although it did inhibit the basal rpS6 phosphorylation. Thus the present study provides the first genetic evidence that S6K1 plays a major role in the development of compensatory renal hypertrophy as well as diabetic renal hypertrophy and indicates that UNX- and diabetes-mediated mTOR activation can selectively activate S6K1 without activating S6K2.

compensatory renal hypertrophy; streptozotocin; mammalian target of rapamycin complex 1 signaling; S6 kinases; rapamycin

This article has been cited by other articles:

				B. J. Siroky and M. Bitzer The growing importance of mTORC1-S6K1 signaling in kidney Am J Physiol Renal Physiol, September 1, 2009; 297(3): F583 - F584. [Full Text] [PDF]