PXD025610

PXD025610 is an original dataset announced via ProteomeXchange.

Title	Targeting endoplasmic reticulum-anchored CRTH2 binding to LARP6 ameliorates organ fibrosis
Description	Excessive deposition of extracellular matrix, mainly collagen protein, is the hallmark of organ fibrosis. The molecular mechanisms of the regulation of fibrotic protein biosynthesis are unclear. Here, we found that chemoattractant receptor homologous molecule expressed on TH2 cells (CRTH2), a cell membrane receptor for prostaglandin (PG) D2, is trafficked to the endoplasmic reticulum (ER) membrane in fibroblasts through Caveolin-1. CRTH2 anchored in the ER with bound collagen mRNA recognition motif (RRM) of La ribonucleoprotein domain family member 6 (LARP6) and promoted the degradation of collagen mRNA in fibroblasts. CRTH2 deficiency increased collagen biosynthesis in fibroblasts and exacerbated injury-induced organ fibrosis in mice, which was rescued by LARP6 depletion. Administration of CRTH2 N-terminal peptide reduced collagen production in fibroblasts by binding to LARP6. Similar to CRTH2, Bumetanide structurally bound to the LARP6 RRM domain, suppressed collagen biosynthesis in fibroblasts and alleviated bleomycin-triggered pulmonary fibrosis in mice. The findings reveal a novel anti-fibrotic function of CRTH2 in the ER membrane via interaction with LARP6, which may represent a therapeutic target for fibrotic diseases.
HostingRepository	iProX
AnnounceDate	2021-04-25
AnnouncementXML	Submission_2023-02-09_20:05:28.409.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Shengkai Zuo
SpeciesList	scientific name: Mus sp.; NCBI TaxID: 10095;
ModificationList	No PTMs are included in the dataset
Instrument	Thermo Fisher Scientific instrument model

Revision	Datetime	Status	ChangeLog Entry
0	2021-04-25 19:07:08	ID requested
1	2021-04-25 19:07:35	announced
⏵ 2	2023-02-09 20:05:29	announced	2023-02-10: Update publication information.

Zuo S, Wang B, Liu J, Kong D, Cui H, Jia Y, Wang C, Xu X, Chen G, Wang Y, Yang L, Zhang K, Ai D, Du J, Shen Y, Yu Y, ER-anchored CRTH2 antagonizes collagen biosynthesis and organ fibrosis via binding LARP6. EMBO J, 40(16):e107403(2021) [pubmed]

submitter keyword: CRTH2, LARP6, Collagen synthesis, Organ fibrosis

Yujun Shen
contact affiliation	Tianjin Medical University
contact email	yujun_shen@tmu.edu.cn
lab head
Shengkai Zuo
contact affiliation	Tianjin Medical University
contact email	zuoshengkai@126.com
dataset submitter

iProX dataset URI