Tamoxifen decreases the myofibroblast count in the healing bile duct tissue of pigs

Siqueira, Orlando Hiroshi Kiono; Filho, Benedito Herani; Paula, Rafael Erthal de; Ascoli, F. O.; Nóbrega, Antônio Cláudio Lucas da; Carvalho, Ângela Cristina Gouvêa; Pires, Andrea; Gaglionone, Nicolle Cavalcante; Cunha, Karin Soares Gonçalves; Granjeiro, José Mauro

doi:10.6061/clinics/2013(01)oa16

Cited by 5 publications

(5 citation statements)

References 43 publications

(41 reference statements)

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“…Tmx reduced the expression of α‐SMA in the healing tissue, suggesting a decrease in myofibroblast number (Siqueira et al . ). In a previous study in a rat model, it was reported that the antifibrotic effects of tmx are associated with reduced TGF‐β1 levels, which in turn is related to the reduction in postoperative adhesion in a dose‐ and time‐dependent manner (Karaca 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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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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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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“…Through Masson staining, we found a large number of collagen fibers and smooth muscle fibers in the anastomotic stoma 1 month after the operation, and the fibers were disorderly and broken. The characteristics of scar formation in CJS are as follows (39)(40)(41): inflammatory cell infiltration and fibroblast activation appeared in the early stage of anastomotic stoma healing; with time, infiltration of inflammatory cells in the anastomotic stoma was gradually aggravated, fibroblasts and myofibroblasts proliferated, and collagen fibers and smooth muscle fibers increased significantly, and eventually led to the proliferation of granulation tissue and scar formation. If an early intervention can reduce the anastomosis's inflammatory reaction and the activation of fibroblasts, it could prevent CJS scars' formation.…”

Section: Discussionmentioning

confidence: 99%

Mechanism of scar formation following Roux-en-Y choledochojejunostomy in a novel rat model of obstructive jaundice

Lyu¹,

Wang²,

Zhou³

et al. 2021

Ann Transl Med

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Background:The present study aimed to analyze the scar formation mechanism following Roux-en-Y choledochojejunostomy (CJS) in a novel rat model of obstructive jaundice. Methods:The biliary obstruction model of Sprague-Dawley (SD) rats was established in advance, and 24 rats were randomly divided into 4 groups (control group, 1-day ligation group, 3-day ligation group, and 5-day ligation group). Changes in postoperative weight, common bile duct diameter, and laboratory indexes were analyzed to determine the best operation time. Roux-en-Y CJS in rats was studied based on the model, and the rats were randomly divided into 4 groups [control group, 3-day choledochojejunostomy (CJS) group, 7-day CJS group, and 30-day CJS group]. The same indexes were analyzed, and the characteristics of scar formation were evaluated by histopathology and polymerase chain reaction examination.Results: The third day after common bile duct ligation is the best time for a Roux-en-Y CJS. The common bile duct diameter expands to 4.2 mm on average, and these physiological characteristics are consistent with current standard clinical findings. After completing CJS, the rats' weight returned to normal levels, and alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (TB), direct bilirubin (DB), and C-reactive protein (CRP) indexes gradually decreased (P<0.05). Anastomotic stoma diameter tended to narrow with time and was significantly narrower on day 30 than preoperation. After CJS, the expression of α-smooth muscle actin (α-SMA) peaked in the early stage and was still higher than that of the control group in the bile duct wall 1 month postoperatively (P<0.05). Transforming growth factor-β1 (TGF-β1) expression gradually increased and was higher than that of the control group at each stage postoperatively (P<0.05). Conclusions:The rat Roux-en-Y CJS model is more in line with our surgical model, and the clinical condition has potential applicability for the study of CJS scar formation. Scar formation following CJS in rats is characterized by the activation of fibroblasts caused by early inflammatory stimulation, which leads to the proliferation of collagen and smooth muscle fibers, resulting in scars.

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“…The present study demonstrated that the transplanted bile duct patch did not survive but went through a process of destruction and regeneration. It is known that epithelial cells and periductal myofibroblasts are closely linked because damage to the former leads to activation and proliferation of the latter ( 23 , 24 ). Ki67 + cuboidal columnar epithelial cells were found within the columnar biliary epithelial and peribiliary glands.…”

Section: Discussionmentioning

confidence: 99%

Establishment of a mouse model for bile duct repair and tissue engineering

Pan

et al. 2022

Exp Ther Med

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Due to the lack of a suitable model, research on biliary biology is far behind that on other organs. A mouse model of common bile duct (CBD) dilation (BDD) was first established and compared with CBD ligation mice (BDL). Then, in a transplantation experiment, the dilated CBD of recipient BDD mice was injured by making an elliptical incision and repaired by transplanting a bile duct patch from donor BDD mice. Biochemical and histological changes were analyzed and cell proliferation of the bile duct grafts was determined. Slightly dilated and unblocked CBD with a diameter of 2.89±0.76 mm was obtained in BDD mice, while the CBD diameter was 0.51±0.08 mm in the Sham group and 4.71±0.64 mm in the BDL group on day 14 after surgery. The liver damage was very mild in BDD mice compared with BDL mice, proving that the BDD model could be further used for bile duct transplantation. By cross transplanting the bile duct patch from enhanced green fluorescence protein and wild-type BDD mice, it was found that the CBD injury was well repaired and the cells of the bile duct patch were completely replaced by recipient-derived cells at 12 week after the repair operation. α Smooth muscle actin, Ki67 and cytokeratin 19 immunofluorescence staining showed that the proliferation of bile duct epithelial cells and abundant active fibroblasts were found within the bile duct patch during the regeneration process. Therefore, a reliable new mouse model of bile duct injury and repair was successfully established and can be used in the study of biliary repair mechanisms and tissue engineering of biliary ducts.

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Tamoxifen decreases the myofibroblast count in the healing bile duct tissue of pigs

Cited by 5 publications

References 43 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

Mechanism of scar formation following Roux-en-Y choledochojejunostomy in a novel rat model of obstructive jaundice

Establishment of a mouse model for bile duct repair and tissue engineering

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