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Protective role of heat shock protein 27 in gastric mucosal injury
Author(s) -
Ebert Matthias PA,
Schäfer Claus,
Chen Jie,
Hoffmann Juliane,
Gu Ping,
Kubisch Constanze,
CarlMcGrath Stacy,
Treiber Gerhard,
Malfertheiner Peter,
Röcken Christoph
Publication year - 2005
Publication title -
the journal of pathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.964
H-Index - 184
eISSN - 1096-9896
pISSN - 0022-3417
DOI - 10.1002/path.1815
Subject(s) - heat shock protein , shock (circulatory) , medicine , chemistry , biochemistry , gene
Heat shock protein 27 (HSP27) mediates cytoprotective effects through its function as a molecular chaperone and through the phosphorylation‐dependent stabilization of actin filaments. The role of HSP27 in gastric ulcer formation and healing is, however, unknown. The expression of HSP27 was studied in human gastric tissue specimens obtained from patients with gastric ulcers and from healthy Helicobacter pylori ‐negative individuals, who received low‐dose aspirin, rofecoxib, and the combination in a prospective study. The susceptibility of the gastric mucosa to indomethacin‐induced lesions was further studied in transgenic mice overexpressing human HSP27 (Tg huHSP27 ) and compared with wild‐type mice (Wt). The expression of HSP27, COX‐1, and COX‐2 was investigated in Tg huHSP27 mice and Wt mice by immunohistochemistry and western blot analysis. While no specific changes in HSP27 expression were found following exposure of healthy human gastric mucosa to oral administration of aspirin or refocoxib, chronic gastric ulcers showed strong HSP27 expression at the ulcer base and margins. Here it was expressed by granulation tissue and regenerating surface epithelium. In Tg huHSP27 mice, overexpression of HSP27 led to a significant decrease of indomethacin‐induced erosions and ulcers compared with Wt mice. COX‐1 and COX‐2 levels did not change. HSP27 is involved in chronic gastric ulcer repair mechanisms in humans, while overexpression of human HSP27 in gastric epithelial cells in mice reduces the susceptibility to non‐steroidal anti‐inflammatory drug (NSAID)‐induced gastric ulceration. This indicates that HSP27 expression is critical for mucosal protection in the stomach. Copyright © 2005 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.