Published online before print April 19, 2007

This Article Full Text Full Text (PDF) All Versions of this Article: ajpath.2007.060899v1 170/6/1854    most recent Purchase Article View Shopping Cart Services Similar articles in this journal Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Sumi, E. Articles by Doi, T. Search for Related Content PubMed Articles by Sumi, E. Articles by Doi, T.

(American Journal of Pathology. 2007;170:1854-1864.)
© 2007 American Society for Investigative Pathology
DOI: 10.2353/ajpath.2007.060899

SRY-Related HMG Box 9 Regulates the Expression of Col4a2 through Transactivating Its Enhancer Element in Mesangial Cells

Eriko Sumi^*, Noriyuki Iehara^*, Haruhiko Akiyama, Takeshi Matsubara^*, Akira Mima^*, Hiroshi Kanamori^*, Atsushi Fukatsu^*, David J. Salant, Toru Kita, Hidenori Arai^¶ and Toshio Doi^||

From the Departments of Nephrology,^* Orthopaedics, Cardiovascular Medicine, and Geriatric Medicine,^¶ Kyoto University Graduate School of Medicine, Kyoto, Japan; the Department of Medicine, Evans Biomedical Research Center, Boston University Medical Center, Boston, Massachusetts; and the Department of Clinical Biology and Medicine,|| Tokushima University School of Medicine, Tokushima, Japan

Accumulation of 1(IV) and 2(IV) collagen is one of the characteristic pathological changes in glomerulosclerosis. Although the Col4a2 gene is known to have a 0.3-kb critical enhancer element with the GAACAAT motif, which transcription factor binds and transactivates this motif has not been identified. In this study, we found that SRY-related HMG box 9 (SOX9) was bound to the GAACAAT motif in the Col4a2 enhancer in vitro and in vivo in mesangial cells. SOX9 strongly activated this enhancer when cotransfected with Col4a2 enhancer-promoter construct in mesangial cells and Swiss/3T3 cells. Mutation in the GAACAAT motif eliminated the activation by SOX9. Furthermore, transforming growth factor-ß (TGF-ß) treatment induced the expression of SOX9 and Col4a2, and a small interfering RNA against SOX9 reduced Col4a2 expression induced by TGF-ß treatment in mesangial cells. In vivo, we found that the expression of SOX9 was dramatically increased along with the expression of TGF-ß and Col4a2 in mouse nephrotoxic nephritis. These results indicate that SOX9 is essential for Col4a2 expression in mesangial cells and might be involved in the accumulation of 2(IV) collagen in experimental nephritis.

This article has been cited by other articles:

				K. Piper Hanley, F. Oakley, S. Sugden, D. I. Wilson, D. A. Mann, and N. A. Hanley Ectopic SOX9 Mediates Extracellular Matrix Deposition Characteristic of Organ Fibrosis J. Biol. Chem., May 16, 2008; 283(20): 14063 - 14071. [Abstract] [Full Text] [PDF]