Effect of Gpnmb expressed in macrophages on repair of injured liver and hepatocarcinogenesis

• Project/Area Number: 26461013
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Gastroenterology
• Research Institution: Kagoshima University
• Principal Investigator: Ido Akio 鹿児島大学, 医歯学域医学系, 教授 (30291545)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2016: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000); Fiscal Year 2015: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2014: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
• Keywords: 急性冠不全 / マクロファージ / 組織修復 / 肝再生 / 肝線維化 / 炎症生発癌 / 急性肝不全 / 炎症性発癌 / 肝繊維化 / 炎症性発がん

Outline of Final Research Achievements

This study aimed to clarify the characteristics of infiltrating macrophages that express Glycoprotein nonmetastatic melanoma B (Gpnmb), and the involvement of Gpnmb in the repair process in response to liver injury. Gpnmb expression in the liver was stimulated four days after CCl4 injection. Gpnmb-positive cells were almost positive for CD68-positive macrophages, contained engulfed apoptotic bodies and exhibited enhanced phagocytic activity. Isolated infiltrating hepatic macrophages transfected with siGpnmb showed high MMP-13 secretion. Hepatic MMP-13 expression, as well as α-SMA expression and collagen production, decreased significantly in mice lacking Gpnmb. Additionally, Gpnmb-positive macrophage infiltrated around inoculated heaptoma nodules. These results indicated that Gpnmb-positive macrophages contribute to the balance between fibrosis and fibrolysis in the repair process, and also play an important role in development of hepatocellular carcinoma.

Research Products

• [Journal Article] Glycoprotein Nonmetastatic Melanoma B (Gpnmb)-Positive Macrophages Contribute to the Balance between Fibrosis and Fibrolysis during the Repair of Acute Liver Injury in Mice (2015)
  • Author(s): Kumagai K, Tabu K, Sasaki F, Takami Y, Morinaga Y, Mawatari S, Hashimoto S, Tanoue S, Kanmura S, Tamai T, Moriuchi A, Uto H, Tsubouchi H, Ido A.
  • Journal Title: PLoS One Volume: 10
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Expression of glycoprotein nonmetastatic melanoma protein B in macrophages infiltrating injured mucosa is associated with severity of experimental colitis in mice (2015)
  • Author(s): Sasaki F, Kumagai K, Uto H, Takami Y, Kure T, Tabu K, Nasu Y, Hashimoto S, Kanmura S, Numata M, Moriuchi A, Sakiyama T, Tsubouchi H, Ido A
  • Journal Title: Molecular Medicine Reports Volume: 12
  • Peer Reviewed / Open Access / Acknowledgement Compliant