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| DOI | 10.1096/fj.202001820R |
| Transcription factor old astrocyte specifically induced substance is a novel regulator of kidney fibrosis | |
| Yamamoto, Ayaha; Morioki, Hitomi; Nakae, Takafumi; Miyake, Yoshiaki; Harada, Takeo; Noda, Shunsuke; Mitsuoka, Sayuri; Matsumoto, Kotaro; Tomimatsu, Masashi; Kanemoto, Soshi; Tanaka, Shota; Maeda, Makiko; Conway, Simon J.; Imaizumi, Kazunori; Fujio, Yasushi; Obana, Masanori | |
| 通讯作者 | Obana, M |
| 来源期刊 | FASEB JOURNAL
 |
| ISSN | 0892-6638 |
| EISSN | 1530-6860 |
| 英文摘要 | Prevention of kidney fibrosis is an essential requisite for effective therapy in preventing chronic kidney disease (CKD). Here, we identify Old astrocyte specifically induced substance (OASIS)/cAMP responsive element-binding protein 3-like 1 (CREB3l1), a CREB/ATF family transcription factor, as a candidate profibrotic gene that drives the final common pathological step along the fibrotic pathway in CKD. Although microarray data from diseased patient kidneys and fibrotic mouse model kidneys both exhibit OASIS/Creb3l1 upregulation, the pathophysiological roles of OASIS in CKD remains unknown. Immunohistochemistry revealed that OASIS protein was overexpressed in human fibrotic kidney compared with normal kidney. Moreover, OASIS was upregulated in murine fibrotic kidneys, following unilateral ureteral obstruction (UUO), resulting in an increase in the number of OASIS-expressing pathological myofibroblasts. In vitro assays revealed exogenous TGF-beta 1 increased OASIS expression coincident with fibroblast-to-myofibroblast transition and OASIS contributed to TGF-beta 1-mediated myofibroblast migration and increased proliferation. Significantly, in vivo kidney fibrosis induced via UUO or ischemia/reperfusion injury was ameliorated by systemic genetic knockout of OASIS, accompanied by reduced myofibroblast proliferation. Microarrays revealed that the transmembrane glycoprotein Bone marrow stromal antigen 2 (Bst2) expression was reduced in OASIS knockout myofibroblasts. Interestingly, a systemic anti-Bst2 blocking antibody approach attenuated kidney fibrosis in normal mice but not in OASIS knockout mice after UUO, signifying Bst2 functions downstream of OASIS. Finally, myofibroblast-restricted OASIS conditional knockouts resulted in resistance to kidney fibrosis. Taken together, OASIS in myofibroblasts promotes kidney fibrosis, at least in part, via increased Bst2 expression. Thus, we have identified and demonstrated that OASIS signaling is a novel regulator of kidney fibrosis. |
| 英文关键词 | chronic kidney disease fibrosis myofibroblast transcription regulation |
| 类型 | Article ; Early Access |
| 语种 | 英语 |
| 开放获取类型 | Other Gold |
| 收录类别 | SCI-E |
| WOS记录号 | WOS:000589711000001 |
| WOS关键词 | RENAL FIBROBLAST ACTIVATION ; EXPRESSION ; OASIS ; MYOFIBROBLASTS ; OASIS/CREB3L1 ; METASTASIS ; TRANSDUCER ; MECHANISMS ; INHIBITION ; MIGRATION |
| WOS类目 | Biochemistry & Molecular Biology ; Biology ; Cell Biology |
| WOS研究方向 | Biochemistry & Molecular Biology ; Life Sciences & Biomedicine - Other Topics ; Cell Biology |
| 资源类型 | 期刊论文 |
| 条目标识符 | http://119.78.100.177/qdio/handle/2XILL650/328490 |
| 作者单位 | [Yamamoto, Ayaha; Morioki, Hitomi; Nakae, Takafumi; Miyake, Yoshiaki; Harada, Takeo; Noda, Shunsuke; Mitsuoka, Sayuri; Matsumoto, Kotaro; Tomimatsu, Masashi; Tanaka, Shota; Fujio, Yasushi; Obana, Masanori] Osaka Univ, Grad Sch Pharmaceut Sci, Lab Clin Sci & Biomed, 1-6 Yamada Oka, Suita, Osaka 5650871, Japan; [Kanemoto, Soshi] Asahikawa Med Univ, Dept Funct Anat & Neurosci, Asahikawa, Hokkaido, Japan; [Maeda, Makiko; Fujio, Yasushi] Osaka Univ, Grad Sch Pharmaceut Sci, Lab Clin Pharmacol & Therapeut, Suita, Osaka, Japan; [Conway, Simon J.] Indiana Univ Sch Med, Herman B Wells Ctr Pediat Res, Indianapolis, IN 46202 USA; [Imaizumi, Kazunori] Hiroshima Univ, Inst Biomed & Hlth Sci, Dept Biochem, Hiroshima, Japan; [Fujio, Yasushi; Obana, Masanori] Osaka Univ, Inst Open & Transdisciplinary Res Initiat OTRI, Integrated Frontier Res Med Sci Div, Suita, Osaka, Japan; [Obana, Masanori] Osaka Univ, Inst Radiat Sci, Radioisotope Res Ctr, Suita, Osaka, Japan |
| 推荐引用方式 GB/T 7714 | Yamamoto, Ayaha,Morioki, Hitomi,Nakae, Takafumi,et al. Transcription factor old astrocyte specifically induced substance is a novel regulator of kidney fibrosis[J]. |
| APA | Yamamoto, Ayaha.,Morioki, Hitomi.,Nakae, Takafumi.,Miyake, Yoshiaki.,Harada, Takeo.,...&Obana, Masanori. |
| MLA | Yamamoto, Ayaha,et al."Transcription factor old astrocyte specifically induced substance is a novel regulator of kidney fibrosis".FASEB JOURNAL |
| 条目包含的文件 | 条目无相关文件。 | |||||
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