AUTHOR=Yang Yang , Zeng Qi-Shan , Zou Min , Zeng Jian , Nie Jiao , Chen DongFeng , Gan Hua-Tian 

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

JOURNAL=Frontiers in Pharmacology

VOLUME=Volume 12 - 2021

YEAR=2021

URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2021.663774

DOI=10.3389/fphar.2021.663774

ISSN=1663-9812

ABSTRACT=Intestinal fibrosis is a consequence in patients who suffered continuous inflammation response that negatively affects life quality of patients. By screening the alter proteomic of mice fibrosis colon, we found Gremlin 1 dramatically up-regulated in fibrotic colon. Further functional experiments revealed that Gremlin 1 could promote the proliferation and activation of intestinal fibroblast cell by enhancing fatty acid oxidation. Blocking Gremlin 1 prevents the progression of intestinal fibrosis in vivo. Mechanism research revealed that Gremlin 1 act as a ligand of VEGFR2 and trigging downstream MAPK signaling, which facilitates the FAO related genes expression, consequently, enhanced fatty acid oxidation. Taken together, our data indicated targeting Gremlin 1 could be a promising therapeutic approach for intestinal fibrosis.