Role of osteopontin in diet-induced brown gallstone formation in rats

• 作者: Jin Chang-Guo Jiang Feng-Ru Zhang Jie Ma Jun-Ren Ling Xiao-Feng
• 来源期刊: 中华医学杂志英文版
• 关键词: Pigment gallstone Rat model Osteopontin TNF-α CYP7A1
• 年，卷（期）: 2021,（9）
• 所属期刊栏目: Original Article
• 页码范围: 1093-1100
• 页数: 8页
• 语种: 中文
• DOI: 10.1097/CM9.0000000000001519

摘要

Background::Although osteopontin (OPN) is expressed in the liver and pigment gallstones of patients with hepatolithiasis, its role in pigment gallstone formation remains unclear. This study aimed to explore the function of OPN in pigment gallstone formation.Methods::Rats were fed a chow diet (CD) or lithogenic diet (LD) for 10 consecutive weeks; blocking tests were then performed using an OPN antibody (OPN-Ab). Incidence of gallstones and levels of several bile components, OPN, tumor necrosis factor alpha (TNF-α), and cholesterol 7 alpha-hydroxylase (CYP7A1) were analyzed. To determine TNF-α expression in hepatic macrophages and both CYP7A1 and bile acid (BA) expression in liver cells, recombinant rat OPN and recombinant rat TNF-α were used to treat rat hepatic macrophages and rat liver cells, respectively. Chi-square or Fisher exact tests were used to analyze qualitative data, Student t-test or one-way analysis of variance were used to analyze qualitative data. Results::Incidence of gallstones was higher in LD-fed rats than in CD-fed rats (80% vs. 10%, P < 0.05). BA content significantly decreased in bile ( t= -36.08, P < 0.01) and liver tissue ( t= -16.16, P < 0.01) of LD-fed rats. Both hepatic OPN protein expression ( t= 9.78, P < 0.01) and TNF-α level ( t= 8.83, P < 0.01) distinctly increased in the LD group; what’s more, CYP7A1 mRNA and protein levels ( t= -12.35, P < 0.01) were markedly down-regulated in the LD group. Following OPN-Ab pretreatment, gallstone formation decreased (85% vs. 25%, χ2 = 14.55, P < 0.01), liver TNF-α expression ( F = 20.36, P < 0.01) was down-regulated in the LD group, and CYP7A1 expression ( F = 17.51, P < 0.01) was up-regulated. Through CD44 and integrin receptors, OPN promoted TNF-α production in macrophage ( F= 1041, P < 0.01), which suppressed CYP7A1 expression ( F = 48.08, P < 0.01) and reduced liver BA synthesis ( F= 119.4, P < 0.01). Conclusions::We provide novel evidence of OPN involvement in pigmented gallstone pathogenesis in rats.