靶向Gremlin 1通过抑制成纤维细胞的脂肪酸氧化来阻止肠道纤维化进展。
Targeting Gremlin 1 Prevents Intestinal Fibrosis Progression by Inhibiting the Fatty Acid Oxidation of Fibroblast Cells.
作者信息
Yang Yang, Zeng Qi-Shan, Zou Min, Zeng Jian, Nie Jiao, Chen DongFeng, Gan Hua-Tian
机构信息
Department of Gastroenterology and the Center of Inflammatory Bowel Disease, West China Hospital, Sichuan University, Chengdu, China.
Lab of Inflammatory Bowel Disease, Clinical Institute of Inflammation and Immunology, Frontiers Science Center for Disease-related Molecular Network, West China Hospital, Sichuan University, Chengdu, China.
出版信息
Front Pharmacol. 2021 Apr 22;12:663774. doi: 10.3389/fphar.2021.663774. eCollection 2021.
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 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.
肠道纤维化是持续炎症反应的结果，会对患者的生活质量产生负面影响。通过筛选小鼠纤维化结肠组织中改变的蛋白质组学图谱，我们发现与正常组织相比，GREM1显著上调。功能实验表明，GREM1通过增强脂肪酸氧化促进肠道成纤维细胞的增殖和活化。阻断GREM1可阻止肠道纤维化的进展。机制研究表明，GREM1作为VEGFR2的配体，触发下游MAPK信号传导。这促进了脂肪酸氧化相关基因的表达，从而增强了脂肪酸氧化。综上所述，我们的数据表明，靶向GREM1可能是治疗肠道纤维化的一种有前景的治疗方法。
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