Periplaneta americana extract attenuates hepatic fibrosis progression by inhibiting collagen synthesis and regulating the TGF-β1/Smad signaling pathway.

IF 1.7 4区 生物学 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY
Folia histochemica et cytobiologica Pub Date : 2023-01-01 Epub Date: 2023-12-11 DOI:10.5603/fhc.94457
Yi Chen, Yanwen Zhao, Liping Yuan, Ying He, Yongshou Yang, Peiyun Xiao
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引用次数: 0

Abstract

Introduction: Liver fibrosis is the damage repair response following chronic liver diseases. Activated hepatic stellate cells (HSCs) are the main extracellular matrix (ECM)-producing cells and key regulators in liver fibrosis. Periplaneta americana shows prominent antifibrotic effects in liver fibrosis; however, the underlying mechanisms remain undetermined. This study aimed to elucidate the therapeutic effects of P. americana extract (PA-B) on liver fibrosis based on the regulation of the TGF-β1/Smad signal pathway.

Material and methods: HSCs and Sprague Dawley rats were treated with TGF-β1 and CCl4, respectively, to establish the hepatic fibrosis model in vitro and in vivo. The effect of PA-B on liver rat fibrosis was evaluated by biochemical (serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), hyaluronic acid (HA), laminin (LN), collagen type IV (Col-IV), pro-collagen type III (PC-III)) and histological examinations. Further, fibrogenic markers expression of alpha smooth muscle actin (α-SMA), collagen type I (Col-I), and collagen type III (Col-III), and the TGF-β1/Smad pathway-related factors were assessed by immunofluorescence (IF), real time quantitative polymerase chain reaction (RT-qPCR), and western blotting (WB).

Results: Treatment of HSC-T6 cells with PA-B suppressed the expression of α-SMA, Col-I, and Col-III, downregulated the expression of TGF-β1 receptors I and II (TβR I and TβR II, respectively), Smad2, and Smad3, and upregulated Smad7 expression. PA-B mitigates pathologic changes in the rat model of liver fibrosis, thus alleviating liver index, and improving liver function and fibrosis indices. The effects of PA-B on the expression of α-SMA, Col-I, Col-III, TβR I, TβR II, Smad2, Smad3, and Smad7 were consistent with the in vitro results, including reduced TGF-β1 expression.

Conclusions: The therapeutic effect of PA-B on liver fibrosis might involve suppression of the secretion and expression of TGF-β1, regulation of the TGF-β1/Smad signaling pathway, and inhibition of collagen production and secretion.

Periplaneta americana 提取物通过抑制胶原蛋白合成和调节 TGF-β1/Smad 信号通路,减轻肝纤维化进展。
导言肝纤维化是慢性肝病后的损伤修复反应。活化的肝星状细胞(HSCs)是细胞外基质(ECM)的主要生成细胞,也是肝纤维化的关键调节因子。Periplaneta americana 对肝纤维化有显著的抗纤维化作用,但其潜在机制仍未确定。材料与方法:分别用TGF-β1和CCl₄处理造血干细胞和Sprague Dawley大鼠,在体外和体内建立肝纤维化模型。通过生化(血清天冬氨酸氨基转移酶(AST)、丙氨酸氨基转移酶(ALT)、透明质酸(HA)、层粘连蛋白(LN)、Ⅳ型胶原蛋白(Col-Ⅳ)、Ⅲ型原胶原蛋白(PC-Ⅲ))和组织学检查评估了 PA-B 对肝脏大鼠纤维化的影响。此外,还通过免疫荧光(IF)、实时定量聚合酶链式反应(RT-qPCR)和免疫印迹(WB)评估了α-平滑肌肌动蛋白(α-SMA)、Ⅰ型胶原蛋白(Col-Ⅰ)和Ⅲ型胶原蛋白(Col-Ⅲ)等纤维化标志物以及TGF-β1/Smad通路相关因子的表达:结果:用 PA-B 处理 HSC-T6 细胞可抑制 α-SMA、Col-I 和 Col-III 的表达,下调 TGF-β1 受体 I 和 II(分别为 TβR I 和 TβR II)、Smad2 和 Smad3 的表达,并上调 Smad7 的表达。PA-B 可减轻大鼠肝纤维化模型的病理变化,从而减轻肝脏指数,改善肝功能和肝纤维化指数。PA-B对α-SMA、Col-I、Col-III、TβR I、TβR II、Smad2、Smad3和Smad7表达的影响与体外实验结果一致,包括降低TGF-β1的表达:结论:PA-B对肝纤维化的治疗作用可能包括抑制TGF-β1的分泌和表达,调节TGF-β1/Smad信号通路,抑制胶原蛋白的产生和分泌。
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来源期刊
Folia histochemica et cytobiologica
Folia histochemica et cytobiologica 生物-生化与分子生物学
CiteScore
2.80
自引率
6.70%
发文量
56
审稿时长
6-12 weeks
期刊介绍: "Folia Histochemica et Cytobiologica" is an international, English-language journal publishing articles in the areas of histochemistry, cytochemistry and cell & tissue biology. "Folia Histochemica et Cytobiologica" was established in 1963 under the title: ‘Folia Histochemica et Cytochemica’ by the Polish Histochemical and Cytochemical Society as a journal devoted to the rapidly developing fields of histochemistry and cytochemistry. In 1984, the profile of the journal was broadened to accommodate papers dealing with cell and tissue biology, and the title was accordingly changed to "Folia Histochemica et Cytobiologica". "Folia Histochemica et Cytobiologica" is published quarterly, one volume a year, by the Polish Histochemical and Cytochemical Society.
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