Severe fibrosis and increased expression of fibrogenic cytokines in the gastric wall of systemic sclerosis patients.
OBJECTIVE
Systemic sclerosis (SSc) is a connective tissue disorder characterized by fibrosis of the skin and internal organs. Although the esophagus is the most frequently affected part of the gastrointestinal tract, all other segments can be involved. The present study was undertaken to evaluate the fibrotic process and the expression of fibrogenic cytokines in the gastric wall of SSc patients with gastroesophageal involvement.


METHODS
Full-thickness surgical and endoscopic gastric biopsy samples were obtained from 14 SSc patients and 10 controls. Tissue sections were either stained with Masson's trichrome or by immunohistochemistry and analyzed for the expression of types I, III, and IV collagen, alpha-smooth muscle actin (alpha-SMA), transforming growth factor beta (TGFbeta), connective tissue growth factor (CTGF), and endothelin 1 (ET-1).


RESULTS
In the gastric wall of SSc patients, Masson's trichrome staining and immunohistochemistry for types I and III collagen revealed a high amount of collagen in the lamina propria that increased toward the muscularis mucosae. In addition, muscle layers showed features of atrophy, with wide areas of focal fibrosis surrounding smooth muscle cells. Type IV collagen was present around glands and small vessels, suggesting a thickening of the basal lamina. The expression of the fibrogenic cytokines TGFbeta and CTGF, ET-1, and the myofibroblast marker alpha-SMA was stronger in SSc patients than in controls.


CONCLUSIONS
A pronounced deposition of collagen, the presence of myofibroblasts, and increased expression of several profibrotic factors are important hallmarks in the stomach of patients with SSc. The fibrotic involvement of the gastric wall may account for muscle atrophy leading to stomach hypomotility in SSc.
Manetti
Mirko
M
University of Florence, Florence, Italy.
Neumann
Elena
E
Milia
Anna Franca
AF
Tarner
Ingo H
IH
Bechi
Paolo
P
Matucci-Cerinic
Marco
M
Ibba-Manneschi
Lidia
L
Müller-Ladner
Ulf
U
D000199:Actins; D000368:Aged; D001706:Biopsy; D016022:Case-Control Studies; D024042:Collagen Type I; D024061:Collagen Type III; D024141:Collagen Type IV; D055513:Connective Tissue Growth Factor; D016207:Cytokines / Q000096:biosynthesis*; D019332:Endothelin-1 / Q000096:biosynthesis; D005260:Female; D005355:Fibrosis; D005773:Gastroscopy; D015870:Gene Expression; D006801:Humans; D017874:Immediate-Early Proteins / Q000096:biosynthesis; D036341:Intercellular Signaling Peptides and Proteins / Q000096:biosynthesis; D008297:Male; D008875:Middle Aged; D012595:Scleroderma, Systemic / Q000276:immunology*; D012720:Severity of Illness Index; D013270:Stomach / Q000473:pathology*; D016212:Transforming Growth Factor beta / Q000096:biosynthesis
D000199:Actins; C526317:CCN2 protein, human; D024042:Collagen Type I; D024061:Collagen Type III; D024141:Collagen Type IV; D016207:Cytokines; D019332:Endothelin-1; D017874:Immediate-Early Proteins; D036341:Intercellular Signaling Peptides and Proteins; D016212:Transforming Growth Factor beta; D055513:Connective Tissue Growth Factor