1. Academic Validation
  2. Hepatocyte growth factor attenuates high glucose-disturbed mitochondrial dynamics in podocytes by decreasing ARF6-dependent DRP1 translocation

Hepatocyte growth factor attenuates high glucose-disturbed mitochondrial dynamics in podocytes by decreasing ARF6-dependent DRP1 translocation

  • Biochim Biophys Acta Mol Cell Res. 2023 Oct 31;1871(1):119623. doi: 10.1016/j.bbamcr.2023.119623.
Yankun Li 1 Xue Li 1 Yuling Yang 1 Fengxia Li 1 Qi Chen 1 Zhonghua Zhao 1 Nong Zhang 1 Hui Li 2
Affiliations

Affiliations

  • 1 Department of Pathology, School of Basic Medical Sciences, Fudan University, Shanghai 200032, China.
  • 2 Department of Pathology, School of Basic Medical Sciences, Fudan University, Shanghai 200032, China. Electronic address: huili78@fudan.edu.cn.
Abstract

Diabetic nephropathy (DN), one of the most common complications of Diabetes Mellitus, is the leading cause of end-stage renal diseases worldwide. Our previous study proved that hepatocyte growth factor (HGF) alleviated renal damages in mice with type 1 Diabetes Mellitus by suppressing overproduction of Reactive Oxygen Species (ROS) in podocytes, while the further mechanism of how HGF lessens ROS production had not been clarified yet. ADP-ribosylation factor 6 (ARF6), the member of the small GTPases superfamilies, is widely spread among epithelial cells and can be activated by the HGF/c-Met signaling. Thus, this study was aimed to explore whether HGF could function on mitochondrial homeostasis, the main resource of ROS, in podocytes exposed to diabetic conditions via ARF6 activation. Our in vivo data showed that HGF markedly ameliorated the pathological damages in kidneys of db/db mice, especially the sharp decline of podocyte number, which was mostly blocked by the ARF6 inhibitor SecinH3. Correspondingly, our in vitro data revealed that HGF protected against high glucose-induced podocyte injuries by increasing ARF6 activity. Besides, this ARF6-dependent beneficial effect of HGF on podocytes was accompanied by improved mitochondrial dynamics and declined DRP1 translocation from cytosol to mitochondria. Collectively, our findings confirm the ability of HGF maintaining mitochondrial homeostasis in diabetic podocytes via decreasing ARF6-dependent DRP1 translocation and shed LIGHT on the novel mechanism of HGF treatment for DN.

Keywords

ADP-ribosylation factor 6; Dynamin related protein 1; Hepatocyte growth factor; Mitochondrial homeostasis; Podocyte.

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