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: 290/1/F223    most recent 00371.2004v1 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 ISI 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 ISI Web of Science (10) Citing Articles via Google Scholar Google Scholar Articles by Moeckel, G. W. Articles by Pozzi, A. Search for Related Content PubMed PubMed Citation Articles by Moeckel, G. W. Articles by Pozzi, A.

Role of integrin ₁₁ in the regulation of renal medullary osmolyte concentration

¹Renal Pathology Division, Department of Pathology and the ²Nephrology Division, Department of Medicine, Vanderbilt School of Medicine and ³Veterans Affairs Hospital, Nashville, Tennessee

Submitted 5 October 2004 ; accepted in final form 2 August 2005

The mechanism by which cells sense extracellular tonicity and trigger the accumulation of protective organic osmolytes is poorly understood. It has been proposed that changes in cell volume following alteration of extracellular toncity are important initiators of signaling events that lead to osmolyte accumulation. Because the extracellular matrix receptors integrins are linked to the cytoskeleton and can transduce signals that alter cell behavior, we investigated the role of these receptors in the modulation of osmolyte accumulation in the kidney medulla under different osmotic conditions. We show that integrin ₁-null mice have impaired ability to accumulate organic osmolytes in the inner medulla due to altered signaling and decreased induction of osmolyte transporters or aldose reductase gene transcription. Utilizing inner medullary collecting duct cells, we demonstrate that the lack of integrin ₁₁ results in an impaired ability to induce the tonicity enhancer-binding protein TonEBP under hypertonic conditions. Furthermore, under the same conditions, integrin ₁-null cells show prolonged ERK1/2 phosphorylation and decreased inositol uptake compared with control cells. The reduction of inositol uptake is significantly reversed by treatment with the MEK inhibitor PD-98059. Finally, integrin ₁-null mice develop morphological changes of early tubular necrosis and increased apoptosis of renal medullary cells following dehydration. Together, these results show that integrin ₁₁ is an important mediator of the compatible osmolyte response in the medulla of the mammalian kidney.

volume regulation; signaling; tonEBP; MAPK

This article has been cited by other articles:

				R. A. Fenton and M. A. Knepper Mouse Models and the Urinary Concentrating Mechanism in the New Millennium Physiol Rev, October 1, 2007; 87(4): 1083 - 1112. [Abstract] [Full Text] [PDF]

				M. B. Burg, J. D. Ferraris, and N. I. Dmitrieva Cellular Response to Hyperosmotic Stresses Physiol Rev, October 1, 2007; 87(4): 1441 - 1474. [Abstract] [Full Text] [PDF]

				R. Padda, A. Wamsley-Davis, M. C. Gustin, R. Ross, C. Yu, and D. Sheikh-Hamad MEKK3-mediated signaling to p38 kinase and TonE in hypertonically stressed kidney cells Am J Physiol Renal Physiol, October 1, 2006; 291(4): F874 - F881. [Abstract] [Full Text] [PDF]

				W. Neuhofer and F.-X. Beck Survival in Hostile Environments: Strategies of Renal Medullary Cells Physiology, June 1, 2006; 21(3): 171 - 180. [Abstract] [Full Text] [PDF]