Connective tissue growth factor is a regulator for fibrosis in human chronic pancreatitis

Fabio F. Di Mola, Helmut Friess, Marcus E. Martignoni, Pierluigi Di Sebastiano, Arthur Zimmermann, Paolo Innocenti, Hans Graber, Leslie I. Gold, Murray Korc, Markus W. Büchler

Research output: Contribution to journalArticle

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Abstract

Objective: To evaluate the parameters that mediate fibrogenesis in chronic pancreatitis (CP). Background: Connective tissue growth factor (CTGF), which is regulated by transforming growth factor β (TGF-β), has recently been implicated in skin fibrosis and atherosclerosis. In the present study, the authors analyzed the concomitant presence of TGF-β1 and its signaling receptors - TGF-β receptor I, subtype ALK5 (TβR-I(ALK5)), and TGF-β receptor II (TβR-II)as well as CTGF and collagen type I in the pancreatic tissue of patients undergoing surgery for chronic pancreatitis. Patients and Methods: CP tissue samples were obtained from 40 patients (8 women, 32 men) undergoing pancreatic resection. Tissue samples of 25 previously healthy organ donors (12 women, 13 men) served as controls. The expression of TGF-β1, TβR-I(ALK5), TβR-II, CTGF, and collagen type I was studied by Northern blot analysis. By in situ hybridization and immunohistochemistry, the respective mRNA moieties and proteins were localized in the tissue samples. Results: Northern blot analysis showed that CP tissue samples exhibited concomitant enhanced mRNA expression of TGF-β1 (38-fold), TβR-II (5-fold), CTGF (25-fold), and collagen type I (24-fold) compared with normal controls. In addition, TβR-I(ALK5) mRNA was increased in 50% of CP tissue samples (1.8-fold). By in situ hybridization, TGF-β1, TβR-I(ALK5), and TβR-II mRNA were often seen to be colocalized, especially in the ductal cells and in metaplastic areas where atrophic acinar cells appeared to dedifferentiate into ductal structures. In contrast, CTGF was located in degenerating acinar cells and principally in fibroblasts surrounding these areas. Moreover, CTGF mRNA expression levels correlated positively with the degree of fibrosis in CP tissues. Conclusion: The concomitant overexpression of CTGF, collagen type I, TGF-β1, and its signaling receptors in CP suggests that these proteins contribute to enhanced extracellular matrix synthesis and accumulation, resulting finally in the fibrogenesis observed in CP.

Original languageEnglish (US)
Pages (from-to)63-71
Number of pages9
JournalAnnals of Surgery
Volume230
Issue number1
DOIs
StatePublished - Jul 1999
Externally publishedYes

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Connective Tissue Growth Factor
Chronic Pancreatitis
Transforming Growth Factors
Fibrosis
Collagen Type I
Messenger RNA
Growth Factor Receptors
Acinar Cells
Northern Blotting
In Situ Hybridization
Extracellular Matrix
Atherosclerosis
Proteins
Fibroblasts
Immunohistochemistry
Tissue Donors
Skin

ASJC Scopus subject areas

  • Surgery

Cite this

Di Mola, F. F., Friess, H., Martignoni, M. E., Di Sebastiano, P., Zimmermann, A., Innocenti, P., ... Büchler, M. W. (1999). Connective tissue growth factor is a regulator for fibrosis in human chronic pancreatitis. Annals of Surgery, 230(1), 63-71. https://doi.org/10.1097/00000658-199907000-00010

Connective tissue growth factor is a regulator for fibrosis in human chronic pancreatitis. / Di Mola, Fabio F.; Friess, Helmut; Martignoni, Marcus E.; Di Sebastiano, Pierluigi; Zimmermann, Arthur; Innocenti, Paolo; Graber, Hans; Gold, Leslie I.; Korc, Murray; Büchler, Markus W.

In: Annals of Surgery, Vol. 230, No. 1, 07.1999, p. 63-71.

Research output: Contribution to journalArticle

Di Mola, FF, Friess, H, Martignoni, ME, Di Sebastiano, P, Zimmermann, A, Innocenti, P, Graber, H, Gold, LI, Korc, M & Büchler, MW 1999, 'Connective tissue growth factor is a regulator for fibrosis in human chronic pancreatitis', Annals of Surgery, vol. 230, no. 1, pp. 63-71. https://doi.org/10.1097/00000658-199907000-00010
Di Mola FF, Friess H, Martignoni ME, Di Sebastiano P, Zimmermann A, Innocenti P et al. Connective tissue growth factor is a regulator for fibrosis in human chronic pancreatitis. Annals of Surgery. 1999 Jul;230(1):63-71. https://doi.org/10.1097/00000658-199907000-00010
Di Mola, Fabio F. ; Friess, Helmut ; Martignoni, Marcus E. ; Di Sebastiano, Pierluigi ; Zimmermann, Arthur ; Innocenti, Paolo ; Graber, Hans ; Gold, Leslie I. ; Korc, Murray ; Büchler, Markus W. / Connective tissue growth factor is a regulator for fibrosis in human chronic pancreatitis. In: Annals of Surgery. 1999 ; Vol. 230, No. 1. pp. 63-71.
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abstract = "Objective: To evaluate the parameters that mediate fibrogenesis in chronic pancreatitis (CP). Background: Connective tissue growth factor (CTGF), which is regulated by transforming growth factor β (TGF-β), has recently been implicated in skin fibrosis and atherosclerosis. In the present study, the authors analyzed the concomitant presence of TGF-β1 and its signaling receptors - TGF-β receptor I, subtype ALK5 (TβR-I(ALK5)), and TGF-β receptor II (TβR-II)as well as CTGF and collagen type I in the pancreatic tissue of patients undergoing surgery for chronic pancreatitis. Patients and Methods: CP tissue samples were obtained from 40 patients (8 women, 32 men) undergoing pancreatic resection. Tissue samples of 25 previously healthy organ donors (12 women, 13 men) served as controls. The expression of TGF-β1, TβR-I(ALK5), TβR-II, CTGF, and collagen type I was studied by Northern blot analysis. By in situ hybridization and immunohistochemistry, the respective mRNA moieties and proteins were localized in the tissue samples. Results: Northern blot analysis showed that CP tissue samples exhibited concomitant enhanced mRNA expression of TGF-β1 (38-fold), TβR-II (5-fold), CTGF (25-fold), and collagen type I (24-fold) compared with normal controls. In addition, TβR-I(ALK5) mRNA was increased in 50{\%} of CP tissue samples (1.8-fold). By in situ hybridization, TGF-β1, TβR-I(ALK5), and TβR-II mRNA were often seen to be colocalized, especially in the ductal cells and in metaplastic areas where atrophic acinar cells appeared to dedifferentiate into ductal structures. In contrast, CTGF was located in degenerating acinar cells and principally in fibroblasts surrounding these areas. Moreover, CTGF mRNA expression levels correlated positively with the degree of fibrosis in CP tissues. Conclusion: The concomitant overexpression of CTGF, collagen type I, TGF-β1, and its signaling receptors in CP suggests that these proteins contribute to enhanced extracellular matrix synthesis and accumulation, resulting finally in the fibrogenesis observed in CP.",
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T1 - Connective tissue growth factor is a regulator for fibrosis in human chronic pancreatitis

AU - Di Mola, Fabio F.

AU - Friess, Helmut

AU - Martignoni, Marcus E.

AU - Di Sebastiano, Pierluigi

AU - Zimmermann, Arthur

AU - Innocenti, Paolo

AU - Graber, Hans

AU - Gold, Leslie I.

AU - Korc, Murray

AU - Büchler, Markus W.

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N2 - Objective: To evaluate the parameters that mediate fibrogenesis in chronic pancreatitis (CP). Background: Connective tissue growth factor (CTGF), which is regulated by transforming growth factor β (TGF-β), has recently been implicated in skin fibrosis and atherosclerosis. In the present study, the authors analyzed the concomitant presence of TGF-β1 and its signaling receptors - TGF-β receptor I, subtype ALK5 (TβR-I(ALK5)), and TGF-β receptor II (TβR-II)as well as CTGF and collagen type I in the pancreatic tissue of patients undergoing surgery for chronic pancreatitis. Patients and Methods: CP tissue samples were obtained from 40 patients (8 women, 32 men) undergoing pancreatic resection. Tissue samples of 25 previously healthy organ donors (12 women, 13 men) served as controls. The expression of TGF-β1, TβR-I(ALK5), TβR-II, CTGF, and collagen type I was studied by Northern blot analysis. By in situ hybridization and immunohistochemistry, the respective mRNA moieties and proteins were localized in the tissue samples. Results: Northern blot analysis showed that CP tissue samples exhibited concomitant enhanced mRNA expression of TGF-β1 (38-fold), TβR-II (5-fold), CTGF (25-fold), and collagen type I (24-fold) compared with normal controls. In addition, TβR-I(ALK5) mRNA was increased in 50% of CP tissue samples (1.8-fold). By in situ hybridization, TGF-β1, TβR-I(ALK5), and TβR-II mRNA were often seen to be colocalized, especially in the ductal cells and in metaplastic areas where atrophic acinar cells appeared to dedifferentiate into ductal structures. In contrast, CTGF was located in degenerating acinar cells and principally in fibroblasts surrounding these areas. Moreover, CTGF mRNA expression levels correlated positively with the degree of fibrosis in CP tissues. Conclusion: The concomitant overexpression of CTGF, collagen type I, TGF-β1, and its signaling receptors in CP suggests that these proteins contribute to enhanced extracellular matrix synthesis and accumulation, resulting finally in the fibrogenesis observed in CP.

AB - Objective: To evaluate the parameters that mediate fibrogenesis in chronic pancreatitis (CP). Background: Connective tissue growth factor (CTGF), which is regulated by transforming growth factor β (TGF-β), has recently been implicated in skin fibrosis and atherosclerosis. In the present study, the authors analyzed the concomitant presence of TGF-β1 and its signaling receptors - TGF-β receptor I, subtype ALK5 (TβR-I(ALK5)), and TGF-β receptor II (TβR-II)as well as CTGF and collagen type I in the pancreatic tissue of patients undergoing surgery for chronic pancreatitis. Patients and Methods: CP tissue samples were obtained from 40 patients (8 women, 32 men) undergoing pancreatic resection. Tissue samples of 25 previously healthy organ donors (12 women, 13 men) served as controls. The expression of TGF-β1, TβR-I(ALK5), TβR-II, CTGF, and collagen type I was studied by Northern blot analysis. By in situ hybridization and immunohistochemistry, the respective mRNA moieties and proteins were localized in the tissue samples. Results: Northern blot analysis showed that CP tissue samples exhibited concomitant enhanced mRNA expression of TGF-β1 (38-fold), TβR-II (5-fold), CTGF (25-fold), and collagen type I (24-fold) compared with normal controls. In addition, TβR-I(ALK5) mRNA was increased in 50% of CP tissue samples (1.8-fold). By in situ hybridization, TGF-β1, TβR-I(ALK5), and TβR-II mRNA were often seen to be colocalized, especially in the ductal cells and in metaplastic areas where atrophic acinar cells appeared to dedifferentiate into ductal structures. In contrast, CTGF was located in degenerating acinar cells and principally in fibroblasts surrounding these areas. Moreover, CTGF mRNA expression levels correlated positively with the degree of fibrosis in CP tissues. Conclusion: The concomitant overexpression of CTGF, collagen type I, TGF-β1, and its signaling receptors in CP suggests that these proteins contribute to enhanced extracellular matrix synthesis and accumulation, resulting finally in the fibrogenesis observed in CP.

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