ミトベ　ミチヒロ   Mitobe Michihiro   三戸部　倫大    所属   医学部 医学科（東京女子医科大学病院）    職種   助教
論文種別	原著
言語種別	英語
査読の有無	査読あり
表題	Reduced Klotho expression level in kidney aggravates renal interstitial fibrosis.
掲載誌名	正式名：American journal of physiology. Renal physiology 略　 称：Am J Physiol Renal Physiol ISSNコード：1522-1466(Electronic)1522-1466(Linking)
巻・号・頁	302(10),pp.F1252-64
著者・共著者	Sugiura Hidekazu†, Yoshida Takumi, Shiohira Shunji, Kohei Junko, Mitobe Michihiro, Kurosu Hiroshi, Kuro-O Makoto, Nitta Kosaku, Tsuchiya Ken
発行年月	2012/05
概要	Renal expression of the klotho gene is markedly suppressed in chronic kidney disease (CKD). Since renal fibrosis is the final common pathology of CKD, we tested whether decreased Klotho expression is a cause and/or a result of renal fibrosis in mice and cultured renal cell lines. We induced renal fibrosis by unilateral ureteral obstruction (UUO) in mice with reduced Klotho expression (kl/+ mice) and compared them with wild-type mice. The UUO kidneys from kl/+ mice expressed significantly higher levels of fibrosis markers such as α-smooth muscle actin (α-SMA), fibronectin, and transforming growth factor-β(1) (TGF-β(1)) than those from wild-type mice. In addition, in cultured renal fibroblast cells (NRK49F), the levels of α-SMA and PAI1 expression were significantly suppressed by addition of recombinant Klotho protein to the medium. The similar effects were observed by a TGF-β(1) receptor inhibitor (ALK5 inhibitor). These observations suggest that low renal Klotho expression enhances TGF-β(1) activity and is a cause of renal fibrosis. On the other hand, TGF-β(1) reduced Klotho expression in renal cultured epithelial cells (inner medullary collecting duct and human renal proximal tubular epithelium), suggesting that low renal Klotho expression is a result of renal fibrosis. Taken together, renal fibrosis can trigger a deterioration spiral of Klotho expression, which may be involved in the pathophysiology of CKD progression.
DOI	10.1152/ajprenal.00294.2011
文献番号	22338084