| Item type |
文献 / Documents(1) |
| 公開日 |
2025-03-07 |
| アクセス権 |
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アクセス権 |
open access |
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アクセス権URI |
http://purl.org/coar/access_right/c_abf2 |
| 資源タイプ |
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資源タイプ識別子 |
http://purl.org/coar/resource_type/c_6501 |
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資源タイプ |
journal article |
| 出版社版DOI |
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関連識別子 |
https://doi.org/10.1074/jbc.M111.244541 |
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関連名称 |
10.1074/jbc.M111.244541 |
| 出版タイプ |
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出版タイプ |
VoR |
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出版タイプResource |
http://purl.org/coar/version/c_970fb48d4fbd8a85 |
| タイトル |
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タイトル |
SOX9 Protein Induces a Chondrogenic Phenotype of Mesangial Cells and Contributes to Advanced Diabetic Nephropathy |
| タイトル別表記 |
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その他のタイトル |
SOX9 Contributes to Advanced DM |
| 著者 |
岸, 誠司
安部, 秀斉
Akiyama, Haruhiko
冨永, 辰也
村上, 太一
美馬, 晶
長井, 幸二郎
Kishi, Fumi
松浦, 元一
Matsubara, Takeshi
Iehara, Noriyuki
Ueda, Otoya
Fukushima, Naoshi
Jishage, Kou-ichi
土井, 俊夫
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| 抄録 |
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内容記述 |
Diabetic nephropathy (DN) is the most important chronic kidney disease. We previously reported that Smad1 transcriptionally regulates the expression of extracellular matrix in DN. Phenotypic change in mesangial cells (MCs) is a key pathologic event in the progression of DN. The aim of this study is to investigate a novel mechanism underlying chondrogenic phenotypic change in MCs that results in the development of DN. MCs showed chondrogenic potential in a micromass culture, and BMP4 induced the expression of chondrocyte markers (SRY-related HMG Box 9 (SOX9) and type II collagen (COL2)). Advanced glycation end products induced the expression of chondrocyte marker proteins downstream from the BMP4-Smad1 signaling pathway in MCs. In addition, hypoxia also induced the expression of BMP4, hypoxia-inducible factor-1α (HIF-1α), and chondrocyte markers. Overexpression of SOX9 caused ectopic expression of proteoglycans and COL2 in MCs. Furthermore, forced expression of Smad1 induced chondrocyte markers as well. Dorsomorphin inhibited these inductions. Glomerular expressions of HIF-1α, BMP4, and chondrocyte markers were observed in diabetic nephropathy mice. These positive stainings were observed in mesangial sclerotic lesions. SOX9 was partially colocalized with HIF-1α and BMP4 in diabetic glomeruli. BMP4 knock-in transgenic mice showed not only similar pathological lesions to DN, but also the induction of chondrocyte markers in the sclerotic lesions. Here we demonstrate that HIF-1α and BMP4 induce SOX9 expression and subsequent chondrogenic phenotype change in DN. The results suggested that the transdifferentiation of MCs into chondrocyte-like cells in chronic hypoxic stress may result in irreversible structural change in DN. |
| 書誌情報 |
en : Journal of Biological Chemistry
巻 286,
号 37,
p. 32162-32169,
発行日 2011-07-27
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| 収録物ID |
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収録物識別子タイプ |
EISSN |
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収録物識別子 |
1083351X |
| 収録物ID |
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収録物識別子タイプ |
PISSN |
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収録物識別子 |
00219258 |
| 収録物ID |
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収録物識別子タイプ |
NCID |
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収録物識別子 |
AA1202441X |
| 出版者 |
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出版者 |
American Society for Biochemistry and Molecular Biology |
| 出版者 |
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出版者 |
Elsevier |
| 権利情報 |
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|
権利情報 |
This is an Open Access article under the CC BY license. |
| EID |
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識別子 |
237208 |
| 言語 |
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|
言語 |
eng |
jbc_286_37_32162.pdf (1.8 MB)
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