ERK5 plays an essential role in gestational beta-cell proliferation

作者：Chen, Congde^*; Wu, Suichun; Lin, Xiaokun; Wu, Dazhou; Fischbach, Shane; Xiao, Xiangwei^*

来源：Cell Proliferation, 2018, 51(3): e12410.

DOI：10.1111/cpr.12410

• N-TERMINAL KINASE
• PRIMARY MECHANISM
• PROTEIN-KINASES
• ADULT PANCREAS
• GROWTH-FACTOR
• MASS
• ACTIVATION
• RECEPTOR
• DEATH
• MICE

ObjectivesRestoring a functional beta-cell mass is a fundamental goal in treating diabetes. A complex signalling pathway network coordinates the regulation of beta-cell proliferation, although a role for ERK5 in this network has not been reported. This question was addressed in this study. @@@ Materials and methodsWe studied the activation of extracellular-signal-regulated kinase 5 (ERK5) in pregnant mice, a well-known mouse model of increased beta-cell proliferation. A specific inhibitor of ERK5 activation, BIX02189, was intraperitoneally injected into the pregnant mice to suppress ERK5 signalling. Beta-cell proliferation was determined by quantification of Ki-67(+) beta cells. Beta-cell apoptosis was determined by TUNEL assay. The extent of beta-cell proliferation was determined by beta-cell mass. The alteration of ERK5 activation and CyclinD1 levels in purified mouse islets was examined by Western blotting. @@@ ResultsExtracellular-signal-regulated kinase 5 phosphorylation, which represents ERK5 activation, was significantly upregulated in islets from pregnant mice. Suppression of ERK5 activation by BIX02189 in pregnant mice significantly reduced beta-cell proliferation, without affecting beta-cell apoptosis, resulting in increases in random blood glucose levels and impairment of glucose response of the mice. ERK5 seemed to activate CyclinD1 to promote gestational beta-cell proliferation. @@@ ConclusionsExtracellular-signal-regulated kinase 5 plays an essential role in the gestational augmentation of beta-cell proliferation. ERK5 may be a promising target for increasing beta-cell mass in diabetes patients.

• 出版日期2018-6
• 单位温州医科大学