Enhanced expression of TGF-βs and their receptors in human acute pancreatitis

Helmut Friess, Zhao Lu, Erick Riesle, Waldemar Uhl, Anne Marie Bründler, Laszlo Horvath, Leslie I. Gold, Murray Korc, Markus W. Büchler

Research output: Contribution to journalArticle

69 Citations (Scopus)

Abstract

Objectives: To determine which mechanisms are involved in pancreatic remodeling, repair, and fibrosis after acute necrotizing pancreatitis (NP) in humans. Summary Background Data: Transforming growth factor betas (TGF-βs) are multifunctional polypeptides that have been implicated in the regulation and formation of extracellular matrix and fibrosis. They exert their functions by binding to specific receptors. In this study, we analyze the expression of TGF-β1, TGF-β2, and TGF-β3 and their receptors type I (Tβ- RI [ALK5]), type II (Tβ-RII), and type III (Tβ-RIII) in NP. Patients: Pancreatic tissue samples were obtained from 6 female and 8 male patients with a median age of 65 years (range, 37 to 77 years) undergoing surgery for NP. The median Ranson score of the patients was 6 (range, 2 to 9). The operation was performed a median 5.5 days (range, 4 to 17 days) after the onset of acute pancreatitis. Pancreatic tissue obtained from 12 previously healthy organ donors (6 male, 6 female; median age of 43 years) served as controls. Methods The expression of TGF-β1, TGF-β2, TGF-β3, Tβ-RI (ALK5), Tβ-RII, Tβ-RIII, and collagen type I mRNA was analyzed by Northern blot analysis. In addition, immunohistochemical analysis using polyclonal antibodies was performed to detect TGF-β1, TGF-β2, TGF-β3, Tβ-RI (ALK5), and Tβ-RII. Results: Northern blot analysis showed an increase in TGF-βs and their receptors in NP tissue samples compared with samples from normal controls. The increase was 3.5-fold for TGF-β1 (p <0.05), 2.7-fold for TGF- β2 (p <0.05), 3.5-fold for TGF-β3 (p <0.05), 10-fold for Tβ-RI (ALK5) (p <0.05), 5.7-fold for Tβ-RII (p <0.05), and 1.4-fold for Tβ-RIII (not significant). Collagen type I mRNA was also markedly increased in NP samples and correlated with the level of TGF-βs. Immunohistochemical analysis demonstrated intense TGF-β1, TGF-β2, TGF-β3, Tβ-RI (ALK5), and Tβ-RII immunoreactivity in the remaining acinar and ductal cells in most NP samples; in the normal control pancreas, there was weak to moderate immunoreactivity for these factors only in some acinar cells and a few ductal cells. Conclusion: The marked increase in expression of TGF-βs and their signaling receptors Tβ-RI (ALK5) and Tβ-RII suggests a role for TGF-βs in the repair process after the onset of NP in humans and raises the possibility that TGF- βs might be involved in tissue remodeling and the fibrotic reaction that occurs in the pancreas after necrosis.

Original languageEnglish (US)
Pages (from-to)95-104
Number of pages10
JournalAnnals of Surgery
Volume227
Issue number1
DOIs
StatePublished - Jan 1998
Externally publishedYes

Fingerprint

Transforming Growth Factor beta Receptors
Pancreatitis
Transforming Growth Factor beta
Acinar Cells
Collagen Type I
Northern Blotting
Pancreas
Fibrosis
Acute Necrotizing Pancreatitis
Messenger RNA
Extracellular Matrix
Necrosis
Tissue Donors
Peptides
Antibodies

ASJC Scopus subject areas

  • Surgery

Cite this

Friess, H., Lu, Z., Riesle, E., Uhl, W., Bründler, A. M., Horvath, L., ... Büchler, M. W. (1998). Enhanced expression of TGF-βs and their receptors in human acute pancreatitis. Annals of Surgery, 227(1), 95-104. https://doi.org/10.1097/00000658-199801000-00014

Enhanced expression of TGF-βs and their receptors in human acute pancreatitis. / Friess, Helmut; Lu, Zhao; Riesle, Erick; Uhl, Waldemar; Bründler, Anne Marie; Horvath, Laszlo; Gold, Leslie I.; Korc, Murray; Büchler, Markus W.

In: Annals of Surgery, Vol. 227, No. 1, 01.1998, p. 95-104.

Research output: Contribution to journalArticle

Friess, H, Lu, Z, Riesle, E, Uhl, W, Bründler, AM, Horvath, L, Gold, LI, Korc, M & Büchler, MW 1998, 'Enhanced expression of TGF-βs and their receptors in human acute pancreatitis', Annals of Surgery, vol. 227, no. 1, pp. 95-104. https://doi.org/10.1097/00000658-199801000-00014
Friess, Helmut ; Lu, Zhao ; Riesle, Erick ; Uhl, Waldemar ; Bründler, Anne Marie ; Horvath, Laszlo ; Gold, Leslie I. ; Korc, Murray ; Büchler, Markus W. / Enhanced expression of TGF-βs and their receptors in human acute pancreatitis. In: Annals of Surgery. 1998 ; Vol. 227, No. 1. pp. 95-104.
@article{11f9e53970644906827f7e1d8095be76,
title = "Enhanced expression of TGF-βs and their receptors in human acute pancreatitis",
abstract = "Objectives: To determine which mechanisms are involved in pancreatic remodeling, repair, and fibrosis after acute necrotizing pancreatitis (NP) in humans. Summary Background Data: Transforming growth factor betas (TGF-βs) are multifunctional polypeptides that have been implicated in the regulation and formation of extracellular matrix and fibrosis. They exert their functions by binding to specific receptors. In this study, we analyze the expression of TGF-β1, TGF-β2, and TGF-β3 and their receptors type I (Tβ- RI [ALK5]), type II (Tβ-RII), and type III (Tβ-RIII) in NP. Patients: Pancreatic tissue samples were obtained from 6 female and 8 male patients with a median age of 65 years (range, 37 to 77 years) undergoing surgery for NP. The median Ranson score of the patients was 6 (range, 2 to 9). The operation was performed a median 5.5 days (range, 4 to 17 days) after the onset of acute pancreatitis. Pancreatic tissue obtained from 12 previously healthy organ donors (6 male, 6 female; median age of 43 years) served as controls. Methods The expression of TGF-β1, TGF-β2, TGF-β3, Tβ-RI (ALK5), Tβ-RII, Tβ-RIII, and collagen type I mRNA was analyzed by Northern blot analysis. In addition, immunohistochemical analysis using polyclonal antibodies was performed to detect TGF-β1, TGF-β2, TGF-β3, Tβ-RI (ALK5), and Tβ-RII. Results: Northern blot analysis showed an increase in TGF-βs and their receptors in NP tissue samples compared with samples from normal controls. The increase was 3.5-fold for TGF-β1 (p <0.05), 2.7-fold for TGF- β2 (p <0.05), 3.5-fold for TGF-β3 (p <0.05), 10-fold for Tβ-RI (ALK5) (p <0.05), 5.7-fold for Tβ-RII (p <0.05), and 1.4-fold for Tβ-RIII (not significant). Collagen type I mRNA was also markedly increased in NP samples and correlated with the level of TGF-βs. Immunohistochemical analysis demonstrated intense TGF-β1, TGF-β2, TGF-β3, Tβ-RI (ALK5), and Tβ-RII immunoreactivity in the remaining acinar and ductal cells in most NP samples; in the normal control pancreas, there was weak to moderate immunoreactivity for these factors only in some acinar cells and a few ductal cells. Conclusion: The marked increase in expression of TGF-βs and their signaling receptors Tβ-RI (ALK5) and Tβ-RII suggests a role for TGF-βs in the repair process after the onset of NP in humans and raises the possibility that TGF- βs might be involved in tissue remodeling and the fibrotic reaction that occurs in the pancreas after necrosis.",
author = "Helmut Friess and Zhao Lu and Erick Riesle and Waldemar Uhl and Br{\"u}ndler, {Anne Marie} and Laszlo Horvath and Gold, {Leslie I.} and Murray Korc and B{\"u}chler, {Markus W.}",
year = "1998",
month = "1",
doi = "10.1097/00000658-199801000-00014",
language = "English (US)",
volume = "227",
pages = "95--104",
journal = "Annals of Surgery",
issn = "0003-4932",
publisher = "Lippincott Williams and Wilkins",
number = "1",

}

TY - JOUR

T1 - Enhanced expression of TGF-βs and their receptors in human acute pancreatitis

AU - Friess, Helmut

AU - Lu, Zhao

AU - Riesle, Erick

AU - Uhl, Waldemar

AU - Bründler, Anne Marie

AU - Horvath, Laszlo

AU - Gold, Leslie I.

AU - Korc, Murray

AU - Büchler, Markus W.

PY - 1998/1

Y1 - 1998/1

N2 - Objectives: To determine which mechanisms are involved in pancreatic remodeling, repair, and fibrosis after acute necrotizing pancreatitis (NP) in humans. Summary Background Data: Transforming growth factor betas (TGF-βs) are multifunctional polypeptides that have been implicated in the regulation and formation of extracellular matrix and fibrosis. They exert their functions by binding to specific receptors. In this study, we analyze the expression of TGF-β1, TGF-β2, and TGF-β3 and their receptors type I (Tβ- RI [ALK5]), type II (Tβ-RII), and type III (Tβ-RIII) in NP. Patients: Pancreatic tissue samples were obtained from 6 female and 8 male patients with a median age of 65 years (range, 37 to 77 years) undergoing surgery for NP. The median Ranson score of the patients was 6 (range, 2 to 9). The operation was performed a median 5.5 days (range, 4 to 17 days) after the onset of acute pancreatitis. Pancreatic tissue obtained from 12 previously healthy organ donors (6 male, 6 female; median age of 43 years) served as controls. Methods The expression of TGF-β1, TGF-β2, TGF-β3, Tβ-RI (ALK5), Tβ-RII, Tβ-RIII, and collagen type I mRNA was analyzed by Northern blot analysis. In addition, immunohistochemical analysis using polyclonal antibodies was performed to detect TGF-β1, TGF-β2, TGF-β3, Tβ-RI (ALK5), and Tβ-RII. Results: Northern blot analysis showed an increase in TGF-βs and their receptors in NP tissue samples compared with samples from normal controls. The increase was 3.5-fold for TGF-β1 (p <0.05), 2.7-fold for TGF- β2 (p <0.05), 3.5-fold for TGF-β3 (p <0.05), 10-fold for Tβ-RI (ALK5) (p <0.05), 5.7-fold for Tβ-RII (p <0.05), and 1.4-fold for Tβ-RIII (not significant). Collagen type I mRNA was also markedly increased in NP samples and correlated with the level of TGF-βs. Immunohistochemical analysis demonstrated intense TGF-β1, TGF-β2, TGF-β3, Tβ-RI (ALK5), and Tβ-RII immunoreactivity in the remaining acinar and ductal cells in most NP samples; in the normal control pancreas, there was weak to moderate immunoreactivity for these factors only in some acinar cells and a few ductal cells. Conclusion: The marked increase in expression of TGF-βs and their signaling receptors Tβ-RI (ALK5) and Tβ-RII suggests a role for TGF-βs in the repair process after the onset of NP in humans and raises the possibility that TGF- βs might be involved in tissue remodeling and the fibrotic reaction that occurs in the pancreas after necrosis.

AB - Objectives: To determine which mechanisms are involved in pancreatic remodeling, repair, and fibrosis after acute necrotizing pancreatitis (NP) in humans. Summary Background Data: Transforming growth factor betas (TGF-βs) are multifunctional polypeptides that have been implicated in the regulation and formation of extracellular matrix and fibrosis. They exert their functions by binding to specific receptors. In this study, we analyze the expression of TGF-β1, TGF-β2, and TGF-β3 and their receptors type I (Tβ- RI [ALK5]), type II (Tβ-RII), and type III (Tβ-RIII) in NP. Patients: Pancreatic tissue samples were obtained from 6 female and 8 male patients with a median age of 65 years (range, 37 to 77 years) undergoing surgery for NP. The median Ranson score of the patients was 6 (range, 2 to 9). The operation was performed a median 5.5 days (range, 4 to 17 days) after the onset of acute pancreatitis. Pancreatic tissue obtained from 12 previously healthy organ donors (6 male, 6 female; median age of 43 years) served as controls. Methods The expression of TGF-β1, TGF-β2, TGF-β3, Tβ-RI (ALK5), Tβ-RII, Tβ-RIII, and collagen type I mRNA was analyzed by Northern blot analysis. In addition, immunohistochemical analysis using polyclonal antibodies was performed to detect TGF-β1, TGF-β2, TGF-β3, Tβ-RI (ALK5), and Tβ-RII. Results: Northern blot analysis showed an increase in TGF-βs and their receptors in NP tissue samples compared with samples from normal controls. The increase was 3.5-fold for TGF-β1 (p <0.05), 2.7-fold for TGF- β2 (p <0.05), 3.5-fold for TGF-β3 (p <0.05), 10-fold for Tβ-RI (ALK5) (p <0.05), 5.7-fold for Tβ-RII (p <0.05), and 1.4-fold for Tβ-RIII (not significant). Collagen type I mRNA was also markedly increased in NP samples and correlated with the level of TGF-βs. Immunohistochemical analysis demonstrated intense TGF-β1, TGF-β2, TGF-β3, Tβ-RI (ALK5), and Tβ-RII immunoreactivity in the remaining acinar and ductal cells in most NP samples; in the normal control pancreas, there was weak to moderate immunoreactivity for these factors only in some acinar cells and a few ductal cells. Conclusion: The marked increase in expression of TGF-βs and their signaling receptors Tβ-RI (ALK5) and Tβ-RII suggests a role for TGF-βs in the repair process after the onset of NP in humans and raises the possibility that TGF- βs might be involved in tissue remodeling and the fibrotic reaction that occurs in the pancreas after necrosis.

UR - http://www.scopus.com/inward/record.url?scp=0031941038&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0031941038&partnerID=8YFLogxK

U2 - 10.1097/00000658-199801000-00014

DO - 10.1097/00000658-199801000-00014

M3 - Article

C2 - 9445116

AN - SCOPUS:0031941038

VL - 227

SP - 95

EP - 104

JO - Annals of Surgery

JF - Annals of Surgery

SN - 0003-4932

IS - 1

ER -