title: Heat shock protein A4 controls cell migration and gastric ulcer healing.
abstract: OBJECTIVE
  Heat shock protein A4 (HSPA4, also called Apg-2), a member of the HSP110 family, regulates the immune response in the gut. Here, we assessed the involvement of HSPA4 in gastric ulcer healing by using fibroblasts from wild-type and HSPA4-deficient mice, a murine gastric ulcer model, and samples from 65 patients with gastric cancer.
  
  
  RESULTS
  HSPA4 expression was inversely correlated with gastric ulcer healing following endoscopic resection of gastric cancer. In the human gastric mucosa, the expression of HSPA4 was inversely correlated with the expression of stromal cell-derived factor 1 (SDF-1), its cognate receptor CXC chemokine receptor 4 (CXCR4), the stromal cell marker vimentin, and the epithelial-mesenchymal transition regulator Twist. HSPA4 was overexpressed in stromal cells as well as in human gastric cancer cells. HSPA4 deficiency increased the expression of SDF-1 and CXCR4, as well as the number of fibroblast-specific protein 1-positive cells, leading to accelerated ulcer healing in the murine gastric ulcer model. Deletion of HSPA4 promoted cell migration in mouse fibroblasts through increased expression of SDF-1 and Twist.
  
  
  CONCLUSIONS
  HSPA4 regulates the expression of SDF-1 and Twist in fibroblasts, thereby controlling gastric ulcer healing.
authors: Department of Gastroenterology and Hepatology, Kinki University Faculty of Medicine, 377-2 Ohno-Higashi, Osaka-Sayama, Osaka, 589-8511, Japan, sakurai@med.kindai.ac.jp.
authors: Toshiharu
authors: T
authors: Sakurai
authors: Hiroshi
authors: H
authors: Kashida
authors: Satoru
authors: S
authors: Hagiwara
authors: Naoshi
authors: N
authors: Nishida
authors: Tomohiro
authors: T
authors: Watanabe
authors: Jun
authors: J
authors: Fujita
authors: Masatoshi
authors: M
authors: Kudo
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D054377:Chemokine CXCL12 / Q000378:metabolism; D004195:Disease Models, Animal; D005347:Fibroblasts / Q000378:metabolism; D005753:Gastric Mucosa / Q000502:physiology / Q000601:surgery; D005773:Gastroscopy; D050957:HSP110 Heat-Shock Proteins / Q000378:metabolism*; D006801:Humans; D051379:Mice; D013276:Stomach Ulcer / Q000378:metabolism*; D051879:Twist-Related Protein 1 / Q000378:metabolism; D014945:Wound Healing
chemical_list: C515255:CXCL12 protein, human; D054377:Chemokine CXCL12; C515256:Cxcl12 protein, mouse; D050957:HSP110 Heat-Shock Proteins; C121993:HSPA4 protein, human; C485680:Hspa4 protein, mouse; D051879:Twist-Related Protein 1
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