MYDGF attenuates podocyte injury and proteinuria by activating Akt/BAD signal pathway in mice with diabetic kidney disease

Aims/hypothesis Myeloid-derived growth factor (MYDGF), mainly secreted by bone marrow-derived cells, has been known to promote glucagon-like peptide-1 production and improve glucose/lipid metabolism in mouse models of diabetes, but little is known about the functions of MYDGF in diabetic kidney dise...

Full description

Saved in:
Bibliographic Details
Published in:Diabetologia 2020-09, Vol.63 (9), p.1916-1931
Main Authors: He, Mingjuan, Li, Yixiang, Wang, Li, Guo, Bei, Mei, Wen, Zhu, Biao, Zhang, Jiajia, Ding, Yan, Meng, Biying, Zhang, Liming, Xiang, Lin, Dong, Jing, Liu, Min, Xiang, Lingwei, Xiang, Guangda
Format: Article
Language:English
Subjects:
AKT protein
Animal models
Apoptosis
Bcl-2 protein
Bone marrow
Desmin
Diabetes
Diabetes mellitus
Diabetic nephropathy
Diaphragm
Gene transfer
Glucagon
Glucagon-like peptide 1
Glucose metabolism
High fat diet
Human Physiology
Internal Medicine
Kidney diseases
Lipid metabolism
Medicine
Medicine & Public Health
Metabolic Diseases
Proteinuria
Streptozocin
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Aims/hypothesis Myeloid-derived growth factor (MYDGF), mainly secreted by bone marrow-derived cells, has been known to promote glucagon-like peptide-1 production and improve glucose/lipid metabolism in mouse models of diabetes, but little is known about the functions of MYDGF in diabetic kidney disease (DKD). Here, we investigated whether MYDGF can prevent the progression of DKD. Methods In vivo experiments, both loss- and gain-of-function strategies were used to evaluate the effect of MYDGF on albuminuria and pathological glomerular lesions. We used streptozotocin-treated Mydgf knockout and wild-type mice on high fat diets to induce a model of DKD. Then, albuminuria, glomerular lesions and podocyte injury were evaluated in Mydgf knockout and wild-type DKD mice treated with adeno-associated virus-mediated Mydgf gene transfer. In vitro and ex vivo experiments, the expression of slit diaphragm protein nephrin and podocyte apoptosis were evaluated in conditionally immortalised mouse podocytes and isolated glomeruli from non-diabetic wild-type mice treated with recombinant MYDGF. Results MYDGF deficiency caused more severe podocyte injury in DKD mice, including the disruption of slit diaphragm proteins (nephrin and podocin) and an increase in desmin expression and podocyte apoptosis, and subsequently caused more severe glomerular injury and increased albuminuria by 39.6% compared with those of wild-type DKD mice ( p  
ISSN:0012-186X
1432-0428
DOI:10.1007/s00125-020-05197-2