Roles and mechanisms of JNK pathway in liver regeneration and tumor formation

2016 Fiscal Year Final Research Report

• Project/Area Number: 26860255
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Experimental pathology
• Research Institution: Asahikawa Medical College
• Principal Investigator: Ooshio Takako 旭川医科大学, 医学部, 助教 (80723238)
• Co-Investigator(Renkei-kenkyūsha): NISHIKAWA Yuji 旭川医科大学, 医学部, 教授 (90208166)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Keywords: JNK / MKK7 / 肝細胞増殖 / 肝修復

Outline of Final Research Achievements

The MKK7 which is an upstream regulator of JNKs is suggested to be involved liver proliferation and regeneration, but roles of MKK7 in liver pathophysiology remain obscure. Here we examined the effects of hepatocyte-specific MKK7 knockout (KO) on liver regeneration and repair processes. After a single injection of CCl4, reparation of the injured liver was delayed in KO mice, despite the extent of liver injury and robust regenerative proliferation of hepatocytes that were comparable to control. In hepatocytic spheroids in collagen gel culture (CGC), MKK7 KO suppressed branching morphogenesis and reduced the expression of transgelin and plasminogen activators. Overexpressed these genes in cultured MKK7 KO hepatocytes rescued the attenuated branching morphogenesis in CGC. Our study demonstrates that hepatic MKK7 has important roles in repair processes following liver injury, possibly through promoting migration and morphogenesis of hepatocytes.

Free Research Field

分子細胞生物学