Changes in the interstitial cells of Cajal in the gallbladder of guinea pigs fed a lithogenic diet

Abstract

Cholesterol cholelithiasis is a common disease and gallbladder hypomotility may underlie its pathogenesis. Interstitial cells of Cajal (ICCs) in the gallbladder serve vital roles in regulating gallbladder motility. The aim of the present study was to investigate changes in gallbladder ICCs during the development of cholesterol cholelithiasis. A total of 40 male guinea pigs were randomly assigned to four groups and fed a standard diet (SD) or lithogenic diet (LD) for 2 or 8 weeks. The LD significantly increased the total cholesterol levels in the serum and bile, as well as the serum levels of high-density lipoprotein-cholesterol and low-density lipoprotein-cholesterol after 2 and 8 weeks. The LD also significantly increased and decreased the number of gallbladder ICCs at 2 and 8 weeks, respectively, by regulating the stem cell factor/C-kit pathway. Moreover, the ultrastructure of gallbladder ICCs was significantly altered after 8 weeks, and the protein expression levels of connexin 43 in the gallbladder were differentially altered after 2 and 8 weeks. Finally, cholecystokinin receptor type A (CCK1R) expression in the gallbladder was assessed. In gallbladder ICCs, its expression was significantly increased and decreased after 2 and 8 weeks, respectively. In conclusion, these results demonstrate that the density, ultrastructure and CCK1R expression levels of gallbladder ICCs are differentially altered at various stages of cholesterol cholelithiasis progression, indicating that gallbladder ICCs may be considered a potential therapeutic target for treatment of cholesterol cholelithiasis.

Pathogenesis of Functional Biliary Pain and Pharmacology of Trimebutin

“…Интересны экспериментальные данные об апоптозе клеток Кахаля в условиях гипернасыщенности желчи, которые есть в том числе и в гладкомышечных клетках желчного пузыря и выполняют функцию передачи сигнала [11]. Это может вносить дополнительный вклад в нарушение моторики.…”

How traditional Chinese medicine can prevent recurrence of common bile duct stones after endoscopic retrograde cholangiopancreatography?

“…With advances in recent research, it has been found that Interstitial Cells of Cajal (ICCs) play an important role in maintaining the normal motility of the gallbladder (Huang et al, 2009;Fu et al, 2021). For example, in guinea pigs with cholesterol cholelithiasis, the density and ultrastructure of ICCs in the gallbladder are altered (Huang et al, 2021). Chronic inflammatory response of the gallbladder also leads to ultrastructural damage of the ICCs which in turn affects the normal physiological function of the gallbladder smooth muscle, resulting in abnormal gallbladder activity (Zhang et al, 2022;Ding et al, 2023).…”

Smooth muscle cells, interstitial cells and neurons in the gallbladder (GB): Functional syncytium of electrical rhythmicity and GB motility (Review)

“…Hypercholesterolemia is an independent risk factor for cholelithiasis, as it may increase biliary cholesterol concentrations, consequently leading to bile crystallization and, ultimately, gallstone formation ( 179 , 180 ). More importantly, cholesterol accumulation strongly damaged the density and ultrastructure of GB ICCs by inhibiting the stem cell factor (SCF)/c-Kit pathway, and disrupted membrane receptor functions of STIN cells, particularly CCK1 receptors ( 181 - 183 ). Due to impaired CCK-induced emptying, the resulting GB stasis provides a microenvironment for excess cholesterol to remain in the lumen; in turn, the elevated cholesterol content further impairs GB emptying ( 184 ).…”