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Published 20 June 2005. doi:10.1083/jcb.200412167
The Rockefeller University Press, 0021-9525 $8.00
JCB, Volume 169, Number 6, 921-928
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Article

Musculin/MyoR is expressed in kidney side population cells and can regulate their function



Keiichi Hishikawa1,2, Takeshi Marumo1,2, Shigeki Miura1, Asato Nakanishi1, Yumi Matsuzaki4,9, Katsunori Shibata1, Tomoko Ichiyanagi1, Hiroko Kohike4,9, Takuya Komori4,9, Ichiro Takahashi6, Osamu Takase5, Naohiko Imai5, Masahiro Yoshikawa1,2, Toshihiko Inowa1,3, Matsuhiko Hayashi5, Toshio Nakaki7, Hiromitsu Nakauchi8, Hideyuki Okano4,9, and Toshiro Fujita1,2

1 Department of Clinical Renal Regeneration, Graduate School of Medicine
2 Department of Internal Medicine, Division of Nephrology and Endocrinology
3 Department of Urology, University of Tokyo, Hongo 7-3-1, Bunkyo-ku, Tokyo 113-8655, Japan
4 Department of Physiology, Keio University School of Medicine, Shionanomachi 35, Shinjuku-ku, Tokyo 160, Japan
5 Department of Internal Medicine, Keio University School of Medicine, Shionanomachi 35, Shinjuku-ku, Tokyo 160, Japan
6 Central Electron Microscopic Laboratory, Teikyo University School of Medicine, Kaga 2-11-1, Itabashi-ku, Tokyo 173, Japan
7 Department of Pharmacology, Teikyo University School of Medicine, Kaga 2-11-1, Itabashi-ku, Tokyo 173, Japan
8 The Institute of Medical Science, University of Tokyo, Shirokanedai 4-6-1, Minato-ku, Tokyo 108, Japan
9 Core Research for Evolutional Science and Technology, Japan Science and Technology Corporation, Tokyo 102-8666, Japan

Correspondence to Keiichi Hishikawa: hishikawa-tky{at}umin.ac.jp

Musculin/MyoR is a new member of basic helix-loop-helix transcription factors, and its expression is limited to skeletal muscle precursors. Here, we report that musculin/MyoR is expressed in adult kidney side population (SP) cells and can regulate their function. SP phenotype can be used to purify stem cell–rich fractions. Microarray analysis clarified that musculin/MyoR was exclusively expressed in kidney SP cells, and the cells resided in the renal interstitial space. Musculin/MyoR-positive cells were decreased in acute renal failure, but infusion of kidney SP cells increased musculin/MyoR-positive cells and improved renal function. Kidney SP cells in reversible acute renal failure expressed a high level of renoprotective factors and leukemia inhibitory factor (LIF), but not in irreversible chronic renal failure. In cultured kidney SP cells, LIF stimulated gene expression of renoprotective factors, and down-regulation of musculin/MyoR augmented LIF-induced gene expression. Our results suggest that musculin/MyoR may play important roles not only in developmental processes but also in regenerative processes in adult tissue.

Abbreviations used in this paper: ABC, ATP-binding cassette; ARF, acute renal failure; bHLH, basic helix-loop-helix; BM, bone marrow-derived mononuclear; BMP, bone morphologic protein; BUN, blood urea nitrogen; CRF, chronic renal failure; HGF, hepatocyte growth factor; LIF, leukemia inhibitory factor; RA, retinoic acid; SP, side population; TSA, trichostatin A.


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