Functional analyses of novel mitochondrial fusion inhibitor HPGBin the regulation of heart and metabolism

本研究对一个新基因--胰腺β细胞增殖相关基因进行了功能分析。我们证实了HPGB作为内源性线粒体融合抑制因子等功能，发现其在氧化应激和吞噬有丝分裂的调节中可能发挥作用，并鉴定了参与其融合抑制活性的氨基酸。此外，我们还培育了在胰腺β细胞或心肌中过表达hpgb的转基因小鼠。对β细胞转基因小鼠的表型分析表明，在2型糖尿病条件下，hPGB促进了β细胞的增殖，并抑制了β细胞中氧化脂质的积累。综上所述，本研究首次揭示了HPGB的生理病理意义。

This study performed functional analyses on a novel gene named hyperplasia-associated gene of pancreatic β-cell (HPGB). We confirmed that HPGB functions as an endogenous mitochondrial fusion inhibitor etc., found its possible roles in the regulation of oxidative stress and mitophagy, and identified amino acids involved in its fusion inhibition activity. In addition, we generated transgenic mice overexpressing HPGB in the pancreatic β-cell or cardiac muscle. Phenotypic analyses of the β-cell transgenic mice suggested that HPGB enhances β-cell proliferation and suppresses oxidative lipids accumulation in β-cells under the type 2 diabetic condition. Taken together, this study firstly revealed the physiopathological significance of HPGB.