Local expressions of TGF-beta1, TGF-beta1RI, CTGF, and Smad-7 in Helicobacter pylori-associated gastritis.
OBJECTIVE
Transforming growth-factor (TGF)-beta1 and Smad-7 play important roles in Helicobacter pylori (H. pylori)-associated gastritis. Connective tissue growth factor (CTGF) can facilitate the TGF-beta/Smad signaling by switching off Smad-7. The purpose of this study was to examine the in situ expressions of these cytokines in the gastric antrum with or without H. pylori infection.


METHODS
Antral specimens from 166 patients (96 M, 70 F, median age 52 years, range 26 to 76 years) were used in this study. H. pylori infection status was determined by histological examination and (UBT) [13C]-urea breath test. Degrees of severity and activity of chronic gastritis were scored for all specimens. Immunohistochemistry was used to demonstrate local expressions of TGF-beta1, TGF-beta1 type 1 receptor (TGF-beta1RI), Smad-7, and CTGF in the gastric antrum.


RESULTS
The results demonstrated that mononuclear cells (MNCs) in lamina propria were the major source of these cytokines. The number of MNCs stained with TGF-beta1, TGF-beta1RI, CTGF, and Smad-7 was significantly higher in H. pylori-positive patients than in H. pylori-negative patients. Furthermore, there was a positive correlation between these cytokine-producing MNCs and the severity of chronic gastritis.


CONCLUSIONS
H. pylori infection is associated with increased expression of TGF-beta1, TGF-beta1RI, Smad-7, and CTGF in the gastric antrum. Our results also suggest that the feed-back loop consisting of TGF-beta1, Smad-7, and CTGF may play an important role in the pathogenesis of H. pylori-associated gastritis.
Li
Zhongwu
Z
Department of Pathology, Peking University School of Oncology, Beijing Cancer Hospital, Beijing, People's Republic of China.
Li
Jiyou
J
D030201:Activin Receptors, Type I / Q000096:biosynthesis*; D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000378:metabolism; D002908:Chronic Disease; D055513:Connective Tissue Growth Factor; D016099:Endoscopy, Gastrointestinal; D005260:Female; D005500:Follow-Up Studies; D005756:Gastritis / Q000378:metabolism* / Q000382:microbiology / Q000473:pathology; D016481:Helicobacter Infections / Q000378:metabolism* / Q000382:microbiology / Q000473:pathology; D016480:Helicobacter pylori / Q000302:isolation & purification*; D006801:Humans; D017874:Immediate-Early Proteins / Q000096:biosynthesis*; D007150:Immunohistochemistry; D018969:Insulin-Like Growth Factor Binding Proteins / Q000378:metabolism; D036341:Intercellular Signaling Peptides and Proteins / Q000096:biosynthesis*; D008297:Male; D008875:Middle Aged; D017346:Protein Serine-Threonine Kinases; D011706:Pyloric Antrum / Q000378:metabolism / Q000382:microbiology; D000077293:Receptor, Transforming Growth Factor-beta Type I; D018125:Receptors, Transforming Growth Factor beta / Q000096:biosynthesis*; D012189:Retrospective Studies; D012720:Severity of Illness Index; D051906:Smad7 Protein / Q000096:biosynthesis*; D053773:Transforming Growth Factor beta1 / Q000096:biosynthesis*
D015415:Biomarkers; C526317:CCN2 protein, human; D017874:Immediate-Early Proteins; D018969:Insulin-Like Growth Factor Binding Proteins; D036341:Intercellular Signaling Peptides and Proteins; D018125:Receptors, Transforming Growth Factor beta; D051906:Smad7 Protein; D053773:Transforming Growth Factor beta1; D055513:Connective Tissue Growth Factor; D017346:Protein Serine-Threonine Kinases; D030201:Activin Receptors, Type I; D000077293:Receptor, Transforming Growth Factor-beta Type I