Expression of transforming growth factor beta1, beta2, and beta3 in chronic, cancer-associated, obstructive pancreatitis.

Abstract

CONTEXT:

Myofibroblasts are considered to play central roles in pancreatic fibrosis. The potent fibrogenic capacities of transforming growth factor betas (TGF-betas) have been emphasized in vitro and in animal studies. However, the roles of TGF-betas in human chronic pancreatitis have not been fully clarified.

OBJECTIVE:

To investigate whether expressions of TGF-betas are related to myofibroblast distribution in chronic, cancer-associated, obstructive pancreatitis (COP).

DESIGN:

Histopathologic studies using hematoxylin-eosin and Elastica-Masson trichrome and immunohistochemical studies using antibodies against alpha-smooth muscle actin (SMA); CD68; TGF-beta1, -beta2, and -beta3; and TGF-beta soluble receptor type II were performed in 19 COP cases and 6 controls. By classifying COP tissues into 3 fibrosis phases by the amount of collagen deposits, immunoreactivities for TGF-betas, histopathologic changes, and myofibroblast distribution were examined for each fibrosis phase.

RESULTS:

Six cases were categorized in the early stage of fibrosis, 8 in the intermediate stage, and 5 in the advanced stage. Immunoreactivities for all 3 isoforms of TGF-beta were observed in occasional myofibroblasts. In the early and intermediate stages, TGF-beta1-expressing macrophages and neutrophils were distributed in the midst of myofibroblasts. TGF-beta2 and TGF-beta3 expressions were observed in ductal structures, sometimes even in sites where no or few myofibroblasts were seen. TGF-beta soluble receptor type II was immunoreactive for myofibroblasts, endothelium, and ductal structures.

CONCLUSIONS:

All 3 isoforms of TGF-betas may contribute to fibrosis in COP. Macrophages and neutrophils may be sources of fibrogenic TGF-beta1. Infiltration of these cells appears to play an important role in the progression of COP fibrosis.

• Authors: Yuki Fukumura, Toshio Kumasaka, Keiko Mitani, Kanae Karita, Koichi Suda
• Journal: Archives of pathology & laboratory medicine (Arch Pathol Lab Med) Vol. 130 Issue 3 Pg. 356-61 (Mar 2006) ISSN: 1543-2165 [Electronic] United States
• PMID: 16519564 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Protein Isoforms
• Transforming Growth Factor beta

Topics

• Aged
• Chronic Disease
• Constriction, Pathologic (etiology, metabolism, pathology)
• Female
• Fibroblasts (metabolism, pathology)
• Fibrosis
• Humans
• Immunohistochemistry
• Male
• Middle Aged
• Pancreatic Ducts
• Pancreatic Neoplasms (complications, metabolism, pathology)
• Pancreatitis (etiology, metabolism, pathology)
• Protein Isoforms
• Transforming Growth Factor beta (metabolism)