Targeting Gremlin 1 Prevents Intestinal Fibrosis Progression by Inhibiting the Fatty Acid Oxidation of Fibroblast Cells

被引：15

作者：

Yang, Yang ^{[1
,2
,3
,4
]}

Zeng, Qi-Shan ^{[1
,2
,3
]}

Zou, Min ^{[1
,2
,3
]}

Zeng, Jian ^{[5
]}

Nie, Jiao ^{[3
,6
,7
]}

Chen, DongFeng ^{[4
]}

Gan, Hua-Tian ^{[1
,2
,3
,6
,7
]}

机构：

[1] Sichuan Univ, West China Hosp, Dept Gastroenterol, Chengdu, Peoples R China

[2] Sichuan Univ, West China Hosp, Ctr Inflammatory Bowel Dis, Chengdu, Peoples R China

[3] Sichuan Univ, Clin Inst Inflammat & Immunol, Frontiers Sci Ctr Dis Related Mol Network, Lab Inflammatory Bowel Dis,West China Hosp, Chengdu, Peoples R China

[4] Army Med Univ, Dept Gastroenterol, Daping Hosp, Chongqing, Peoples R China

[5] Chongqing Tradit Chinese Med Hosp, Dept Gastroenterol, Chongqing, Peoples R China

[6] Sichuan Univ, Dept Geriatr, West China Hosp, Chengdu, Peoples R China

[7] Sichuan Univ, Natl Clin Res Ctr Geriatr, West China Hosp, Chengdu, Peoples R China

来源：

FRONTIERS IN PHARMACOLOGY | 2021年 / 12卷

基金：

中国国家自然科学基金;

关键词：

intestinal fibrosis; gremlin; 1; fibroblast cell; fatty acid oxidation; VEGFR2; METASTASIS; EXPRESSION; TGF-BETA-1; PROMOTE; BONE;

D O I：

10.3389/fphar.2021.663774

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

Intestinal fibrosis is a consequence of continuous inflammatory responses that negatively affect the quality of life of patients. By screening altered proteomic profiles of mouse fibrotic colon tissues, we identified that GREM1 was dramatically upregulated in comparison to that in normal tissues. Functional experiments revealed that GREM1 promoted the proliferation and activation of intestinal fibroblast cells by enhancing fatty acid oxidation. Blocking GREM1 prevented the progression of intestinal fibrosis in vivo. Mechanistic research revealed that GREM1 acted as a ligand for VEGFR2 and triggered downstream MAPK signaling. This facilitated the expression of FAO-related genes, consequently enhancing fatty acid oxidation. Taken together, our data indicated that targeting GREM1 could represent a promising therapeutic approach for the treatment of intestinal fibrosis.

引用

页数：13

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