ER-anchored CRTH2 antagonizes collagen biosynthesis and organ fibrosis via binding LARP6

doi:10.15252/embj.2020107403

	ER-anchored CRTH2 antagonizes collagen biosynthesis and organ fibrosis via binding LARP6
	Zuo, Shengkai 1; Wang, Bei 1; Liu, Jiao 1; Kong, Deping 1; Cui, Hui2 ; Jia, Yaonan 3; Wang, Chenyao 4; Xu, Xin 1; Chen, Guilin 1; Wang, Yuanyang 1; Yang, Linlin 5; Zhang, Kai 6; Ai, Ding 7; Du, Jie 8,9; Shen, Yujun 1; Yu, Ying 1
	2021-08-16
发表期刊	EMBO JOURNAL (IF:9.4[JCR-2023],11.0[5-Year])
ISSN	0261-4189
EISSN	1460-2075
DOI	10.15252/embj.2020107403
摘要	Excessive deposition of extracellular matrix, mainly collagen protein, is the hallmark of organ fibrosis. The molecular mechanisms regulating fibrotic protein biosynthesis are unclear. Here, we find that chemoattractant receptor homologous molecule expressed on TH2 cells (CRTH2), a plasma membrane receptor for prostaglandin D2, is trafficked to the endoplasmic reticulum (ER) membrane in fibroblasts in a caveolin-1-dependent manner. ER-anchored CRTH2 binds the collagen mRNA recognition motif of La ribonucleoprotein domain family member 6 (LARP6) and promotes the degradation of collagen mRNA in these cells. In line, CRTH2 deficiency increases collagen biosynthesis in fibroblasts and exacerbates injury-induced organ fibrosis in mice, which can be rescued by LARP6 depletion. Administration of CRTH2 N-terminal peptide reduces collagen production by binding to LARP6. Similar to CRTH2, bumetanide binds the LARP6 mRNA recognition motif, suppresses collagen biosynthesis, and alleviates bleomycin-triggered pulmonary fibrosis in vivo. These findings reveal a novel anti-fibrotic function of CRTH2 in the ER membrane via the interaction with LARP6, which may represent a therapeutic target for fibrotic diseases.
关键词	collagen synthesis CRTH2 LARP6 organ fibrosis
收录类别	SCIE
语种	英语
WOS研究方向	Biochemistry & Molecular Biology ; Cell Biology
WOS类目	Biochemistry & Molecular Biology ; Cell Biology
WOS记录号	WOS:000669501000001
出版者	WILEY
原始文献类型	Article; Early Access
引用统计	正在获取...
文献类型	期刊论文
条目标识符	https://kms.shanghaitech.edu.cn/handle/2MSLDSTB/127730
专题	生命科学与技术学院_博士生
通讯作者	Shen, Yujun; Yu, Ying
作者单位	1.Tianjin Med Univ, Prov & Minist Cosponsored Collaborat Innovat Ctr, Minist Educ,Key Lab Immune Microenvironm & Dis,Ti, Dept Pharmacol,Sch Basic Med Sci,Ctr Cardiovasc D, Tianjin, Peoples R China; 2.Shanghai Tech Univ, Sch Life Sci & Technol, Shanghai, Peoples R China; 3.Zhengzhou Univ, Sch Pharmaceut Sci, Zhengzhou, Peoples R China; 4.Cleveland Clin, Lerner Res Inst, Dept Inflammat & Immun, Cleveland, OH 44106 USA; 5.Zhengzhou Univ, Sch Basic Med Sci, Dept Pharmacol, Zhengzhou, Peoples R China; 6.Tianjin Med Univ, Sch Basic Med Sci, Dept Biochem & Mol Biol, Tianjin, Peoples R China; 7.Tianjin Med Univ, Sch Basic Med Sci, Dept Physiol & Pathophysiol, Tianjin, Peoples R China; 8.Capital Med Univ, Beijing Anzhen Hosp, Beijing, Peoples R China; 9.Beijing Inst Heart Lung & Blood Vessel Dis, Beijing, Peoples R China
推荐引用方式 GB/T 7714	Zuo, Shengkai,Wang, Bei,Liu, Jiao,et al. ER-anchored CRTH2 antagonizes collagen biosynthesis and organ fibrosis via binding LARP6[J]. EMBO JOURNAL,2021.
APA	Zuo, Shengkai.,Wang, Bei.,Liu, Jiao.,Kong, Deping.,Cui, Hui.,...&Yu, Ying.(2021).ER-anchored CRTH2 antagonizes collagen biosynthesis and organ fibrosis via binding LARP6.EMBO JOURNAL.
MLA	Zuo, Shengkai,et al."ER-anchored CRTH2 antagonizes collagen biosynthesis and organ fibrosis via binding LARP6".EMBO JOURNAL (2021).