Submitted on November 13, 2006
Accepted on January 21, 2007
Expression of MAK-V/Hunk in Renal Distal Tubules and Its Possible Involvement in Proliferative Suppression
Masashi Sakai1, KOUICHI TAMURA1*, Yuko Tsurumi1, Yutaka Tanaka1, Yuichi Koide1, Miyuki Matsuda1, Tomoaki Ishigami1, Machiko Yabana1, Yasuo Tokita2, Yukio Hiroi3, Issei Komuro4, and Satoshi Umemura1
1 Dept. of Medical Sci. & Cardiorenal Med., Yokohama City Univ. Graduate Sch. of Med., Yokohama, Japan
2 Renal Division, Department of Medicine, Fujisawa Municipal Hospital, Fujisawa, Japan
3 Vascular Medicine Research, Brigham and Women's Hospital, Harvard Medical School, Cambridge, Massachusetts, United States
4 Department of Cardiovascular Science and Medicine, Chiba University Graduate School of Medicine,, Chiba, Japan
* To whom correspondence should be addressed. E-mail: tamukou{at}med.yokohama-cu.ac.jp.
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 (TAL) 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 as compared to 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 angiotensin II (Ang II)-induced stimulation of c-fos gene transcription, and suppressed the Ang II-mediated increases in transforming growth factor-
(TGF-) 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.
