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This Article Full Text Full Text (PDF) All Versions of this Article: 292/5/F1526    most recent 00451.2006v1 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 ISI Web of Science (1) Citing Articles via Google Scholar Google Scholar Articles by Sakai, M. Articles by Umemura, S. Search for Related Content PubMed PubMed Citation Articles by Sakai, M. Articles by Umemura, S.

Expression of MAK-V/Hunk in renal distal tubules and its possible involvement in proliferative suppression

¹Department of Medical Science and Cardiorenal Medicine, Yokohama City University Graduate School of Medicine, Yokohama; ²Renal Division, Department of Medicine, Fujisawa Municipal Hospital, Fujisawa; ⁴Department of Cardiovascular Science and Medicine, Chiba University Graduate School of Medicine, Chiba, Japan; and ³Vascular Medicine Research, Brigham and Women's Hospital, Harvard Medical School, Cambridge, Massachusetts

Submitted 13 November 2006 ; accepted in final form 21 January 2007

MAK-V/Hunk is an SNF1-related serine/threonine kinase which was previously shown to be highly expressed in the mammary gland and central nervous system. In this study, we found MAK-V/Hunk is abundantly and specifically expressed in the thick ascending limbs and distal convoluted tubules (DCT) of the kidney from the embryonic stage to the adult stage. We demonstrated that dietary salt depletion significantly enhances renal MAK-V/Hunk mRNA levels compared with a normal-salt diet. To analyze the possible renal cellular function of this kinase, we employed mouse distal convoluted tubule (mDCT) cells. The results of reverse transcriptase-polymerase chain reaction and Western blot analysis revealed that MAK-V/Hunk is expressed endogenously in mDCT cells. Overexpression of MAK-V/Hunk by adenoviral gene transfer significantly inhibited the ANG II-induced stimulation of c-fos gene transcription and suppressed the ANG II-mediated increases in transforming growth factor- production into the medium. This phenomenon was accompanied by inhibition of ANG II-induced activation of BrdU incorporation. On the other hand, the MAK-V/Hunk knockdown by siRNA activated the ANG II-induced c-fos gene expression. In the consecutive sections stained for MAK-V/Hunk and AT₁ receptor, MAK-V/Hunk-immunopositive distal tubules expressed the AT₁ receptor. This is the first report on the intrarenal localization of MAK-V/Hunk and its cellular function in renal tubular cells.

SNF1 protein kinase; angiotensin II; transforming growth factor-; renal epithelial cell