AHCC inhibited hepatic stellate cells activation by regulation of cytoglobin induction via TLR2-SAPK/JNK pathway and collagen production via TLR4-NF-κβ pathway.

IF 3.9 3区 医学 Q1 GASTROENTEROLOGY & HEPATOLOGY American journal of physiology. Gastrointestinal and liver physiology Pub Date : 2024-12-01 Epub Date: 2024-09-24 DOI:10.1152/ajpgi.00134.2024
Hayato Urushima, Tsutomu Matsubara, Gu Qiongya, Atsuko Daikoku, Misako Takayama, Chiho Kadono, Hikaru Nakai, Yukinobu Ikeya, Hideto Yuasa, Kazuo Ikeda
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Abstract

Cirrhosis, which represents the end stage of liver fibrosis, remains a life-threatening condition without effective treatment. Therefore, prevention of the progression of liver fibrosis through lifestyle habits such as diet and exercise is crucial. The functional food AHCC, a standardized extract of cultured Lentinula edodes mycelia produced by Amino Up Co., Ltd. (Sapporo, Japan)] has been reported to be effective in improving the pathophysiology of various liver diseases. In this study, the aim was to analyze the influence of AHCC on hepatic stellate cells, which are responsible for liver fibrosis. Eight-week-old male C57BL6/j mice were induced with liver fibrosis by intraperitoneal injection of carbon tetrachloride. Simultaneously, they were orally administered 3% AHCC to investigate its impact on the progression of liver fibrosis. Using the human hepatic stellate cell (HHSteC) line, we analyzed the influence of AHCC on the expression of molecules related to hepatic stellate cell activation. The administration of AHCC resulted in reduced expression of collagen1a, α smooth muscle actin (αSMA), and heat shock protein 47 in the liver. Furthermore, the expression of cytoglobin, a marker for quiescent hepatic stellate cells, was enhanced. In vitro study, it was confirmed that AHCC inhibited αSMA by inducing cytoglobin via upregulating the stress-activated protein kinase/Jun NH2-terminal kinase (SAPK/JNK) pathway through Toll-like receptor (TLR) 2. In addition, AHCC suppressed collagen1a production by hepatic stellate cells through TLR4-NF-κβ pathway. AHCC was suggested to suppress hepatic fibrosis by inhibition of hepatic stellate cells activation. Daily intake of AHCC from mild fibrotic stages may have the potential to prevent the progression of liver fibrosis.NEW & NOTEWORTHY AHCC, a standardized extract of cultured Lentinula edodes mycelia, suppresses liver fibrosis progression by induction of cytoglobin via the Toll-like receptor 2 (TLR2)-stress-activated protein kinase/Jun NH2-terminal kinase (SAPK/JNK) pathway and the inhibition of collagen production via the TLR4-NFκβ pathway in hepatic stellate cells. Daily oral administration of AHCC from the stage of MASLD may have the potential to prevent disease progression to MASH with fibrosis.

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AHCCⓇ通过TLR2-SAPK/JNK途径调节细胞色素诱导和TLR4-NFκB途径调节胶原蛋白生成,从而抑制肝星状细胞的活化。
[导言] 肝硬化是肝纤维化的终末阶段,如果得不到有效治疗,仍会危及生命。因此,通过饮食和运动等生活习惯预防肝纤维化的进展至关重要。据报道,功能性食品AHCCⓇ能有效改善各种肝病的病理生理学。本研究旨在分析 AHCCⓇ对造成肝纤维化的肝星状细胞的影响。[材料与方法] 通过腹腔注射四氯化碳诱导八周大雄性 C57BL6/j 小鼠肝纤维化。同时给小鼠口服 3% AHCCⓇ,以研究其对肝纤维化进展的影响。我们利用人体肝星状细胞系 HHSteC 分析了 AHCCⓇ对肝星状细胞活化相关分子表达的影响。[结果]服用 AHCCⓇ 后,肝脏中胶原蛋白 1a、α 平滑肌肌动蛋白(αSMA)和热休克蛋白 47 的表达量减少。此外,静止肝星状细胞的标志物--细胞血红蛋白的表达也有所增强。体外研究证实,AHCCⓇ通过收费样受体(TLR)2上调SAPK/JNK途径,通过诱导细胞血红蛋白来抑制αSMA。 此外,AHCCⓇ还通过TLR4-NFκβ途径抑制肝星状细胞产生胶原蛋白1a。[结论] AHCCⓇ可通过抑制肝星状细胞的活化来抑制肝纤维化。从轻度肝纤维化阶段开始每天摄入 AHCCⓇ,可能具有防止肝纤维化恶化的潜力。
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来源期刊
CiteScore
9.40
自引率
2.20%
发文量
104
审稿时长
1 months
期刊介绍: The American Journal of Physiology-Gastrointestinal and Liver Physiology publishes original articles pertaining to all aspects of research involving normal or abnormal function of the gastrointestinal tract, hepatobiliary system, and pancreas. Authors are encouraged to submit manuscripts dealing with growth and development, digestion, secretion, absorption, metabolism, and motility relative to these organs, as well as research reports dealing with immune and inflammatory processes and with neural, endocrine, and circulatory control mechanisms that affect these organs.
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Simultaneous optical imaging of gastric slow waves and contractions in the in vivo porcine stomach. Parenteral nutrition results in peripheral ileal to hepatic circadian discordance in mice. AHCC inhibited hepatic stellate cells activation by regulation of cytoglobin induction via TLR2-SAPK/JNK pathway and collagen production via TLR4-NF-κβ pathway. Formal degree programs in physiology promote careers of clinical scientists and benefit basic science departments. Hepatic bile acid accretion correlates with cholestatic liver injury and therapeutic response in Cyp2c70 knockout mice with a humanized bile acid composition.
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