Heat Shock Protein A4 Controls Cell Migration and Gastric Ulcer Healing

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• 作者：Toshiharu Sakurai ; Hiroshi Kashida ; Satoru Hagiwara…
• 关键词：HSP ; SDF ; 1 ; CXCR4 ; Twist ; FSP ; 1 ; Gastric cancer
• 刊名：Digestive Diseases and Sciences
• 出版年：2015
• 出版时间：April 2015
• 年：2015
• 卷：60
• 期：4
• 页码：850-857
• 全文大小：6,990 KB
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• 作者单位：Toshiharu Sakurai (1)
  Hiroshi Kashida (1)
  Satoru Hagiwara (1)
  Naoshi Nishida (1)
  Tomohiro Watanabe (2)
  Jun Fujita (3)
  Masatoshi Kudo (1)
  
  1. Department of Gastroenterology and Hepatology, Kinki University Faculty of Medicine, 377-2 Ohno-Higashi, Osaka-Sayama, Osaka, 589-8511, Japan
  2. Center for Innovation in Immunoregulative Technology and Therapeutics, Kyoto University Graduate School of Medicine, Kyoto, Japan
  3. Department of Clinical Molecular Biology, Kyoto University Graduate School of Medicine, Kyoto, Japan
  
• 刊物类别：Medicine
• 刊物主题：Medicine & Public Health
  Gastroenterology
  Hepatology
  Oncology
  Transplant Surgery
  Biochemistry
  
• 出版者：Springer Netherlands
• ISSN：1573-2568

文摘

Aims and Methods 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. Conclusion HSPA4 regulates the expression of SDF-1 and Twist in fibroblasts, thereby controlling gastric ulcer healing.