BACKGROUND: The etiopathogenesis of cholecystolithiasis is not well defined. Primary dysmotility of the organ, due to fibrosis of the gallbladder wall or muscular dysfunction, is suggested as a crucial factor. Transforming growth factor-beta (TGF-beta) and connective tissue growth factor (CTGF) are involved in several fibrotic disorders and play a critical role in fibrogenesis, thereby changing the physiological function of the organs. In the present study we analyzed the role of TGF-beta and its downstream target CTGF in patients with cholecystolithiasis. METHODS: Gallbladders were obtained from 16 individuals undergoing surgery for symptomatic cholecystolithiasis. Normal human gallbladder tissue samples from five individuals without any history of gallbladder disease were obtained through an organ donor transplantation program. Northern blot analysis, in situ hybridization, and immunohistochemistry were used to analyze the expression of TGF-beta1 and CTGF in the gallbladder tissue samples. RESULTS: By northern blot analysis there was an enhanced TGF-beta1 mRNA expression (eightfold increase; P < 0.04) in the cholecystolithiasis tissue samples in comparison with normal controls. There was also a concomitant increase in CTGF (41-fold increase; P < 0.01). By in situ hybridization and immunohistochemistry, CTGF mRNA was localized mainly in the mucosa layer, while intensive staining of the smooth muscle cells with TGF-beta1 and CTGF was observed. In addition, TGF-beta1 immunoreactivity was also localized in the fibroblasts and inflammatory cells. TGF-beta1 m-RNA levels showed a significant relationship with the degree of fibrosis in the tissue samples (P < 0.04, r = 0.5). CONCLUSION: Our data indicate that TGF-beta and CTGF are involved in ultrastructural tissue changes in patients with cholecystolithiasis. Activation of the "TGF-beta pathway," predominantly in the remaining mucosa and submucosal layer, indicates that extracellular matrix (ECM) synthesis with subsequent gallbladder wall fibrosis is an important step in gallbladder dysfunction in this disorder.
BACKGROUND: The etiopathogenesis of cholecystolithiasis is not well defined. Primary dysmotility of the organ, due to fibrosis of the gallbladder wall or muscular dysfunction, is suggested as a crucial factor. Transforming growth factor-beta (TGF-beta) and connective tissue growth factor (CTGF) are involved in several fibrotic disorders and play a critical role in fibrogenesis, thereby changing the physiological function of the organs. In the present study we analyzed the role of TGF-beta and its downstream target CTGF in patients with cholecystolithiasis. METHODS: Gallbladders were obtained from 16 individuals undergoing surgery for symptomatic cholecystolithiasis. Normal human gallbladder tissue samples from five individuals without any history of gallbladder disease were obtained through an organ donor transplantation program. Northern blot analysis, in situ hybridization, and immunohistochemistry were used to analyze the expression of TGF-beta1 and CTGF in the gallbladder tissue samples. RESULTS: By northern blot analysis there was an enhanced TGF-beta1 mRNA expression (eightfold increase; P < 0.04) in the cholecystolithiasis tissue samples in comparison with normal controls. There was also a concomitant increase in CTGF (41-fold increase; P < 0.01). By in situ hybridization and immunohistochemistry, CTGF mRNA was localized mainly in the mucosa layer, while intensive staining of the smooth muscle cells with TGF-beta1 and CTGF was observed. In addition, TGF-beta1 immunoreactivity was also localized in the fibroblasts and inflammatory cells. TGF-beta1 m-RNA levels showed a significant relationship with the degree of fibrosis in the tissue samples (P < 0.04, r = 0.5). CONCLUSION: Our data indicate that TGF-beta and CTGF are involved in ultrastructural tissue changes in patients with cholecystolithiasis. Activation of the "TGF-beta pathway," predominantly in the remaining mucosa and submucosal layer, indicates that extracellular matrix (ECM) synthesis with subsequent gallbladder wall fibrosis is an important step in gallbladder dysfunction in this disorder.
Authors: Fabio F di Mola; Helmut Friess; Erick Riesle; Alexander Koliopanos; Peter Büchler; Zhaowen Zhu; David R Brigstock; Murray Korc; Markus W Büchler Journal: Ann Surg Date: 2002-01 Impact factor: 12.969
Authors: F F di Mola; H Friess; A Scheuren; P Di Sebastiano; H Graber; B Egger; A Zimmermann; M Korc; M W Büchler Journal: Ann Surg Date: 1999-01 Impact factor: 12.969
Authors: B S Oemar; A Werner; J M Garnier; D D Do; N Godoy; M Nauck; W März; J Rupp; M Pech; T F Lüscher Journal: Circulation Date: 1997-02-18 Impact factor: 29.690
Authors: Ioannis M Stylianou; Jason P Affourtit; Keith R Shockley; Robert Y Wilpan; Fadi A Abdi; Sanjeev Bhardwaj; Jarod Rollins; Gary A Churchill; Beverly Paigen Journal: Genetics Date: 2008-02-03 Impact factor: 4.562
Authors: Kirk J Maurer; Varada P Rao; Zhongming Ge; Arlin B Rogers; Trisha J Oura; Martin C Carey; James G Fox Journal: Gastroenterology Date: 2007-10 Impact factor: 22.682