Yoshimine Haruhito, Tanoue Shiroh, Ibi Yutaro, Minami Masato, Nakahara Mai, Tokunaga Koki, Kanmura Shuji, Ido Akio
Digestive and Lifestyle Diseases, Kagoshima University Graduate School of Medical and Dental Sciences, 8-35-1, Sakuragaoka, Kagoshima, 890-8520, Japan.
Clin Exp Nephrol. 2021 Sep;25(9):935-943. doi: 10.1007/s10157-021-02067-y. Epub 2021 Apr 28.
Peritoneal dialysis (PD) is essential for patients with end-stage renal disease. Peritoneal fibrosis (PF) is a complex inflammatory, fibrogenic process. No effective treatments are available to prevent these processes. Hepatocyte growth factor (HGF) possesses anti-inflammatory and anti-fibrotic properties. The aim of this study was to analyze whether HGF suppresses MGO-induced peritoneal inflammation and fibrosis in a mouse model.
PF was induced by intraperitoneal (IP) injections of MGO for 14 days. C57/BL/6 mice were divided into three groups: Sham group (only vehicle); Sham + MGO group (PF induced by MGO); and HGF + MGO group (PF mice treated with recombinant human-HGF). PF was assessed from tissue samples by Masson's trichrome staining. Inflammation and fibrosis-associated factors were assessed by immunohistochemistry and quantitative real-time PCR.
MGO-injected mice showed significant thickening of the submesothelial compact zone with PF. Treatment with HGF significantly reduced PM thickness and suppressed the expression of collagen I and III and α-SMA. Expression of profibrotic and proinflammatory cytokines (TGF-β, TNF-α, IL-1β) was reduced by HGF treatment. The number of macrophages, and M1 and M2 macrophage-related markers, such as CD86, CD206, and CD163, was reduced in HGF + MGO mice.
HGF attenuates MGO-induced PF in mice. Furthermore, HGF treatment reduces myofibroblast and macrophage infiltration, and attenuates the upregulated expression of proinflammatory and profibrotic genes in peritoneal tissues. HGF might be an effective approach to prevent the development of PF in patients undergoing PD.
腹膜透析（PD）对终末期肾病患者至关重要。腹膜纤维化（PF）是一个复杂的炎症、纤维化过程。目前尚无有效的治疗方法来预防这些过程。肝细胞生长因子（HGF）具有抗炎和抗纤维化特性。本研究的目的是分析HGF是否能在小鼠模型中抑制甲基乙二醛（MGO）诱导的腹膜炎症和纤维化。
通过腹腔内（IP）注射MGO 14天诱导PF。将C57/BL/6小鼠分为三组：假手术组（仅注射溶剂）；假手术+MGO组（由MGO诱导PF）；以及HGF+MGO组（用重组人HGF治疗的PF小鼠）。通过Masson三色染色从组织样本中评估PF。通过免疫组织化学和定量实时PCR评估炎症和纤维化相关因子。
注射MGO的小鼠显示出PF导致的间皮下致密区明显增厚。HGF治疗显著降低了腹膜厚度，并抑制了I型和III型胶原蛋白以及α-平滑肌肌动蛋白（α-SMA）的表达。HGF治疗降低了促纤维化和促炎细胞因子（转化生长因子-β、肿瘤坏死因子-α、白细胞介素-1β）的表达。HGF+MGO小鼠中的巨噬细胞数量以及M1和M2巨噬细胞相关标志物（如CD86、CD206和CD163）减少。
HGF可减轻小鼠中MGO诱导的PF。此外，HGF治疗减少了肌成纤维细胞和巨噬细胞浸润，并减轻了腹膜组织中促炎和促纤维化基因的上调表达。HGF可能是预防接受PD治疗患者发生PF的有效方法。
