Department of Colorectal & Anal Surgery, Guangzhou First People's Hospital, School of Medicine, South China University of Technolgy, Guangzhou, Guangdong, China.
Department of Surgery, Jinling Hospital, Medical School of Nanjing University, Nanjing, Jiangsu, China.
Int Immunopharmacol. 2020 Jun;83:106456. doi: 10.1016/j.intimp.2020.106456. Epub 2020 Apr 1.
Follistatin-like protein 1 (FSTL1) is a pleiotropic cytokine involved in multiple processes including organ development, carcinogenesis, metastasis and so on. Some recent studies have suggested a possible role of FSTL1 in the inflammatory diseases. We for the first time tried to unravel its effect on the colitis, and explore the possible mechanisms. Here we found that FSTL1 was upregulated in active human and murine colitis. It facilitated proinflammatory M1 polarization of macrophages and inhibited the M2 anti-inflammatory phenotype, leading to excessive production of multiple inflammatory cytokines in vitro and in vivo. Haplodeletion of FSTL1 in mice significantly reduced the clinical and histological activity of colitis. Most importantly, macrophage depletion diminished the difference between DSS-treated WT and FSTL1 mice. Altogether, our results suggested that FSTL1 may also serve as an important contributor in the colonic inflammation. The possible mechanism may be related to its modulation on macrophage polarization.
卵泡抑素样蛋白 1（Follistatin-like protein 1，FSTL1）是一种多功能细胞因子，参与多个过程，包括器官发育、癌症发生、转移等。一些最近的研究表明，FSTL1 可能在炎症性疾病中发挥作用。我们首次试图阐明其在结肠炎中的作用，并探讨可能的机制。在这里，我们发现 FSTL1 在活动性人类和鼠类结肠炎中上调。它促进了巨噬细胞的促炎 M1 极化，并抑制了 M2 抗炎表型，导致体外和体内多种炎症细胞因子的过度产生。FSTL1 单倍型缺失的小鼠显著减轻了结肠炎的临床和组织学活动。最重要的是，巨噬细胞耗竭减少了 DSS 处理的 WT 和 FSTL1 小鼠之间的差异。总之，我们的结果表明，FSTL1 也可能作为结肠炎症的一个重要贡献者。其可能的机制与其对巨噬细胞极化的调节有关。
