BubR1 Insufficiency Impairs Liver Regeneration in Aged Mice after Hepatectomy through Intercalated Disc Abnormality

• DOI: 10.1038/srep32399
• Publication Date: 2016-08-26T10:02:45Z
• Authors: Ayae Ikawa-Yoshida; Takuya Matsumoto; Shinji Okano; Yukihiko Aoyagi; Yutaka Matsubara; Tadashi Furuyama; Yoshimichi Nakatsu; Teruhisa Tsuzuki; Mitsuho Onimaru; Tomoko Ohkusa; Masatoshi Nomura; Yoshihiko Maehara
• Keywords: Liver Regeneration; Mitotic index

Abstract A delay in liver regeneration after partial hepatectomy (PHx) leads to acute injury, and such delays are frequently observed aged patients. BubR1 (budding uninhibited by benzimidazole-related 1) controls chromosome mitotic segregation through the spindle assembly checkpoint, down-regulation promotes aging-associated phenotypes. In this study we investigated effects of insufficiency on mice. Low -BubR1 -expressing mutant ( L/L ) mice had a delayed recovery weight-to-body weight ratio increased deviation enzyme levels PHx. Microscopic observation mouse showed an number necrotic hepatocytes intercalated disc anomalies, resulting widened inter-hepatocyte perisinusoidal spaces, smaller early-stage microvilli atrophy. Up-regulation desmocollin-1 (DSC1) was wild-type, but not , addition, knockdown expression caused DSC1 human keratinocyte cell line. results impaired weakened microstructural adaptation against PHx, enhanced transient failure hepatocyte proliferation. Thus, our data suggest that reduction causes abnormality.