Department of Rheumatology, Firat University School of Medicine, Elazig, Turkey.
Department of Rheumatology, Fethi Sekin City Hospital, Elazig, Turkey.
Sci Rep. 2022 Feb 15;12(1):2553. doi: 10.1038/s41598-022-06581-1.
Janus kinase (JAK)-signal transducer and activator of transcription (STAT) pathway is important in the process of inflammation and fibrosis. The adenosine 5'-monophosphate-activated protein kinase (AMPK) enzyme can affect JAK/STAT pathway. Tofacitinib is a pan-JAK inhibitör. Metformin activates AMPK enzyme. We aimed to investigate the therapeutic efficacy of tofacitinib and metformin on IL-17 and TGF-β cytokines, skin fibrosis and inflammation in mouse model of systemic sclerosis (SSc). 40 Balb/c female mice were divided into 4 groups: (control, sham (BLM), tofacitinib and metformin). The mice in the tofacitinib group received oral tofacitinib (20 mg/kg/daily) and mice in the metformin group received oral metformin (50 mg/kg/day) for 28 days. At the end of 4th week, all groups of mice were decapitated and tissue samples were taken for analysis. Histopathological analysis of skin tissue was performed, and mRNA expressions of collagen 3A, IL-17 and TGF-β were assessed by real-time PCR and ELISA. Repeated BLM injections had induced dermal fibrosis. Moreover, the tissue levels of collagen 3A, IL-17 and TGF-β were elevated in the BLM group. Tofacitinib and metformin mitigated dermal fibrosis. They reduced dermal thickness and tissue collagen 3A, IL-17 and TGF-β levels. Tofacitinib and metformin demonstrated anti-inflammatory and anti-fibrotic effects in the mouse model of SSc.
Janus 激酶（JAK）-信号转导和转录激活因子（STAT）通路在炎症和纤维化过程中很重要。腺苷 5'-单磷酸激活蛋白激酶（AMPK）酶可以影响 JAK/STAT 通路。托法替尼是一种泛 JAK 抑制剂。二甲双胍激活 AMPK 酶。我们旨在研究托法替尼和二甲双胍对白细胞介素 17（IL-17）和转化生长因子-β（TGF-β）细胞因子、皮肤纤维化和系统性硬化症（SSc）小鼠模型炎症的治疗效果。40 只雌性 Balb/c 小鼠被分为 4 组：（对照组、假手术（BLM）组、托法替尼组和二甲双胍组）。托法替尼组小鼠口服托法替尼（20mg/kg/天），二甲双胍组小鼠口服二甲双胍（50mg/kg/天），共 28 天。第 4 周末，所有组别的小鼠均被断头处死，采集组织样本进行分析。对皮肤组织进行组织病理学分析，并通过实时 PCR 和 ELISA 评估胶原 3A、IL-17 和 TGF-β 的 mRNA 表达。重复 BLM 注射可诱导皮肤纤维化。此外，BLM 组组织中胶原 3A、IL-17 和 TGF-β 的水平升高。托法替尼和二甲双胍可减轻皮肤纤维化。它们可降低皮肤厚度和组织中胶原 3A、IL-17 和 TGF-β 的水平。托法替尼和二甲双胍在 SSc 小鼠模型中表现出抗炎和抗纤维化作用。
