Role of transforming growth factor-beta signaling pathway in pathogenesis of benign biliary stricture

End-to-end anastomosis in the treatment for bile duct injury during laparoscopic cholecystectomy has been associated with stricture formation. The aim of this study was to experimentally investigate the effect of oral tamoxifen (tmx) treatment on fibrosis, collagen content and transforming growth factor-β1, -β2 and -β3 expression in common bile duct anastomosis of pigs. Twenty-six pigs were divided into three groups [sham (n = 8), control (n = 9) and tmx (n = 9)]. The common bile ducts were transected and anastomosed in the control and tmx groups. Tmx (40 mg/day) was administered orally to the tmx group, and the animals were euthanized after 60 days. Fibrosis was analysed by Masson's trichrome staining. Picrosirius red was used to quantify the total collagen content and collagen type I/III ratio. mRNA expression of transforming growth factor (TGF)-β1, -β2 and -β3 was quantified using real-time polymerase chain reaction (qRT-PCR). The control and study groups exhibited higher fibrosis than the sham group, and the study group showed lower fibrosis than the control group (P = 0.011). The control and tmx groups had higher total collagen content than the sham group (P = 0.003). The collagen type I/III ratio was higher in the control group than in the sham and tmx groups (P = 0.015). There were no significant differences in the mRNA expression of TGF-β1, -β2 and -β3 among the groups (P > 0.05). Tmx decreased fibrosis and prevented the change in collagen type I/III ratio caused by the procedure.

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“…In a previous study, high expression of TGF‐β1 was observed in the stenotic bile duct tissue of 23 patients (Geng et al . ).…”

Section: Discussionmentioning

confidence: 97%

Effect of tamoxifen on fibrosis, collagen content and transforming growth factor‐β1, ‐β2 and ‐β3 expression in common bile duct anastomosis of pigs

Siqueira

Oliveira

Carvalho

et al. 2017

Int J Experimental Path

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“…We also observed a significant amount of fibrotic tissue deposition in the liver biopsies of BDI patients. In the literature, there is one report on increased Smad7 levels in tissue biopsies[ 36 ]. In this study, we were limited to analyzing only mRNA expression, and the expression of Smad7 and of ECM proteins need to be measured in BDI patients.…”

Section: Discussionmentioning

confidence: 99%

Liver fibrosis secondary to bile duct injury: correlation of Smad7 with TGF-β and extracellular matrix proteins

et al. 2009

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BackgroundLiver fibrosis is the result of continuous liver injury stemming from different etiological factors. Bile duct injury induces an altered expression of TGF-β, which has an important role in liver fibrosis because this cytokine induces the expression of target genes such as collagens, PAI-1, TIMPs, and others that lead to extracellular matrix deposition. Smad7 is the principal inhibitor that regulates the target gene transcription of the TGF-β signaling. The aim of the study was to determine whether Smad7 mRNA expression correlates with the gene expression of TGF-β, Col I, Col III, Col IV, or PAI-1 in liver fibrosis secondary to bile duct injury (BDI).ResultsSerum TGF-β concentration was higher in BDI patients (39 296 pg/ml) than in liver donors (9008 pg/ml). Morphometric analysis of liver sections showed 41.85% of tissue contained fibrotic deposits in BDI patients. mRNA expression of Smad7, Col I, and PAI-1 was also significantly higher (P < 0.05) in patients with BDI than in controls. Smad7 mRNA expression correlated significantly with TGF-β concentration, Col I and Col III expression, and the amount of fibrosis.ConclusionWe found augmented serum concentration of TGF-β and an increase in the percentage of fibrotic tissue in the liver of BDI patients. Contrary to expected results, the 6-fold increase in Smad7 expression did not inhibit the expression of TGF-β, collagens, and PAI-1. We also observed greater expression of Col I and Col III mRNA in BDI patients and significant correlations between their expression and TGF-β concentration and Smad7 mRNA expression.

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“…TGF‐β serves an important function in the pathogenesis of biliary strictures . In contrast to a rapidly ascending TNF‐α, the TGF‐β1 changed in a slower and longer duration.…”

Section: Resultsmentioning

confidence: 99%

Delayed rearterialization unlikely leads to nonanastomotic stricture but causes temporary injury on bile duct after liver transplantation

et al. 2014

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Nonanastomotic strictures (NAS) are common biliary complications after liver transplantation (LT). Delayed rearterialization induces biliary injury in several hours. However, whether this injury can be prolonged remains unknown. The correlation of this injury with NAS occurrence remains obscure. Different delayed rearterialization times were compared using a porcine LT model. Morphological and functional changes in bile canaliculus were evaluated by transmission electron microscopy and real-time PCR. Immunohistochemistry and TUNEL were performed to validate intrahepatic bile duct injury. Three months after LT was performed, biliary duct stricture was determined by cholangiography; the tissue of common bile duct was detected by real-time PCR. Bile canaliculi were impaired in early postoperative stage and then exacerbated as delayed rearterialization time was prolonged. Nevertheless, damaged bile canaliculi could fully recover in subsequent months. TNF-α and TGF-β expressions and apoptosis cell ratio increased in the intrahepatic bile duct only during early postoperative period in a time-dependent manner. No abnormality was observed by cholangiography and common bile duct examination after 3 months. Delayed rearterialization caused temporary injury to bile canaliculi and intrahepatic bile duct in a time-dependent manner. Injury could be fully treated in succeeding months. Solo delayed rearterialization cannot induce NAS after LT.

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Role of transforming growth factor-beta signaling pathway in pathogenesis of benign biliary stricture

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Cited by 10 publications

References 26 publications

Effect of tamoxifen on fibrosis, collagen content and transforming growth factor‐β1, ‐β2 and ‐β3 expression in common bile duct anastomosis of pigs

Effect of tamoxifen on fibrosis, collagen content and transforming growth factor‐β1, ‐β2 and ‐β3 expression in common bile duct anastomosis of pigs

Liver fibrosis secondary to bile duct injury: correlation of Smad7 with TGF-β and extracellular matrix proteins

Delayed rearterialization unlikely leads to nonanastomotic stricture but causes temporary injury on bile duct after liver transplantation

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