Klotho protects against diabetic kidney disease via AMPK- and ERK-mediated autophagy

Xue, Meng1; Yang, Feng2; Le, Ying1; Yang, Yanlin2; Wang, Bingsen1; Jia, Yijie2; Zheng, Zongji2; Xue, Yaoming2

2021-05-01

10.1007/s00592-021-01736-4

ACTA DIABETOLOGICA   影响因子和分区

0940-5429

1432-5233

Background Diabetic kidney disease (DKD) is a serious complication of diabetes mellitus and results in serious public health problems. Although a great number of studies have been performed to elucidate the mechanisms of this disease, these mechanisms remain largely unknown. Methods Cell and animal models were first constructed using human renal proximal tubule cells stimulated by high glucose (HG) and mice induced by streptozotocin (STZ). After Klotho overexpression, Klotho expression was assessed by RT-PCR and western blot, immunofluorescence; autophagy and AMPK/ERK proteins were confirmed using western blot or immunohistochemical assay; the autophagosomes were observed by transmission electron microscope; the pathological structure, fibrosis, polysaccharides and glycogen of kidney were evaluated by H&E staining, Masson staining and PAS staining. Results We first confirmed that Klotho expression and autophagic activity were reduced in DM mice and HG-induced human renal proximal tubule cells. Besides, overexpression of Klotho could significantly enhance autophagy and AMPK and ERK1/2 activities in vivo and in vitro, which also could be abolished by selective AMPK inhibitor and ERK activator. Moreover, we proved that Klotho could inhibit hyperglycemia-induced renal tubular damage. Conclusion In summary, our results proved that Klotho improved renal tubular cell autophagy via the AMPK and ERK pathways and played a role in renal protection. These findings provide new insight into the mechanism of Klotho and autophagy in DKD.

Diabetic kidney disease Klotho Autophagy AMPK ERK

SCI

英语

第一

National Natural Science Foundation of China[81870570,81900378]

Endocrinology & Metabolism

Endocrinology & Metabolism

WOS:000655447800001

SPRINGER-VERLAG ITALIA SRL

BIOLOGY & BIOCHEMISTRY

Web of Science

1.Southern Univ Sci & Technol, Shenzhen Peoples Hosp Jinan Univ, Dept Endocrinol & Metab, Clin Med Coll 2,Affiliated Hosp 1, Shenzhen 518020, Peoples R China
2.Southern Med Univ, Nanfang Hosp, Dept Endocrinol & Metab, Guangzhou 510515, Peoples R China

Xue, Meng,Yang, Feng,Le, Ying,et al. Klotho protects against diabetic kidney disease via AMPK- and ERK-mediated autophagy[J]. ACTA DIABETOLOGICA,2021.

Xue, Meng.,Yang, Feng.,Le, Ying.,Yang, Yanlin.,Wang, Bingsen.,...&Xue, Yaoming.(2021).Klotho protects against diabetic kidney disease via AMPK- and ERK-mediated autophagy.ACTA DIABETOLOGICA.

Xue, Meng,et al."Klotho protects against diabetic kidney disease via AMPK- and ERK-mediated autophagy".ACTA DIABETOLOGICA (2021).