Protective role of heat shock protein 27 in gastric mucosal injury.
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.
Ebert
Matthias P A
MP
Department of Gastroenterology, Hepatology and Infectious Diseases, Otto-von-Guericke University, Magdeburg, Germany. Matthias.Ebert@medizin.uni-magdeburg.de
Schäfer
Claus
C
Chen
Jie
J
Hoffmann
Juliane
J
Gu
Ping
P
Kubisch
Constanze
C
Carl-McGrath
Stacy
S
Treiber
Gerhard
G
Malfertheiner
Peter
P
Röcken
Christoph
C
D000368:Aged; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects / Q000627:therapeutic use; D001241:Aspirin / Q000009:adverse effects / Q000627:therapeutic use; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D004359:Drug Therapy, Combination; D004847:Epithelial Cells / Q000378:metabolism; D005260:Female; D005753:Gastric Mucosa / Q000737:chemistry*; D006360:Heat-Shock Proteins / Q000032:analysis*; D016481:Helicobacter Infections / Q000150:complications / Q000188:drug therapy / Q000378:metabolism; D016480:Helicobacter pylori / Q000302:isolation & purification; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D007213:Indomethacin / Q000008:administration & dosage / Q000009:adverse effects; D007274:Injections, Intraperitoneal; D007783:Lactones / Q000009:adverse effects / Q000627:therapeutic use; D008297:Male; D008565:Membrane Proteins; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D011446:Prospective Studies; D011451:Prostaglandin-Endoperoxide Synthases / Q000032:analysis; D013276:Stomach Ulcer / Q000188:drug therapy / Q000209:etiology / Q000378:metabolism*; D013450:Sulfones / Q000009:adverse effects / Q000627:therapeutic use
D000894:Anti-Inflammatory Agents, Non-Steroidal; D006360:Heat-Shock Proteins; D007783:Lactones; D008565:Membrane Proteins; D013450:Sulfones; C116926:rofecoxib; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; C496511:PTGS1 protein, human; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases; C496512:Ptgs1 protein, mouse; D001241:Aspirin; D007213:Indomethacin