VEGF-B antibody and interleukin-22 fusion protein ameliorates diabetic nephropathy through inhibiting lipid accumulation and inflammatory responses.
10.1016/j.apsb.2020.07.002
- Author:
Yilan SHEN
1
;
Wei CHEN
2
;
Lei HAN
2
;
Qi BIAN
1
;
Jiajun FAN
2
;
Zhonglian CAO
2
;
Xin JIN
2
;
Tao DING
1
;
Zongshu XIAN
2
;
Zhiyong GUO
1
;
Wei ZHANG
3
;
Dianwen JU
2
;
Xiaobin MEI
1
Author Information
1. Department of Nephrology, Changhai Hospital, Second Military Medical University, Shanghai 200433, China.
2. Department of Biological Medicines, Fudan University School of Pharmacy, Shanghai 201203, China.
3. Department of Nephrology, Shanghai Yangpu Hospital of TCM, Shanghai 200090, China.
- Publication Type:Journal Article
- Keywords:
ACR, urine albumin-to-creatinine ratio;
ADFP, adipocyte differentiation-related protein;
AGEs, advanced glycation end products;
ALT, alanine aminotransferase;
AST, aspartate aminotransferase;
BUN, blood urea nitrogen;
Ccr, creatinine clearance rate;
DN, diabetic nephropathy;
Diabetic nephropathy;
ECM, extracellular matrix;
ESRD, end-stage renal disease;
FA, fatty acid;
FATPs, fatty acid transport proteins;
Fusion protein;
GBM, glomerular basement membrane;
GSEA, gene set enrichment analysis;
H&E, hematoxylin & eosin;
HbA1c%, glycosylated hemoglobin;
IL-22, interleukin-22;
Interleukin-22;
KEGG, Kyoto Encyclopedia of Genes and Genomes;
NAC, N-acetyl-l-cysteine;
NLRP3, NOD-like receptor family pyrin domain-containing protein 3;
NRP-1, neuropilin-1;
PAS, periodic acid-Schiff;
ROS, reactive oxygen species;
SDS-PAGE, SDS-polyacrylamide gel electrophoresis;
TEM, transmission electron microscopy;
VEGF-B, vascular endothelial growth factor B;
VEGFR, vascular endothelial growth factor receptor;
Vascular endothelial growth factor B;
eGFR, estimated glomerular filtration rate;
β2-MG, β2 microglobulin
- From:
Acta Pharmaceutica Sinica B
2021;11(1):127-142
- CountryChina
- Language:English
-
Abstract:
Diabetic nephropathy (DN) is considered the primary causes of end-stage renal disease (ESRD) and is related to abnormal glycolipid metabolism, hemodynamic abnormalities, oxidative stress and chronic inflammation. Antagonism of vascular endothelial growth factor B (VEGF-B) could efficiently ameliorate DN by reducing renal lipotoxicity. However, this pharmacological strategy is far from satisfactory, as it ignores numerous pathogenic factors, including anomalous reactive oxygen species (ROS) generation and inflammatory responses. We found that the upregulation of VEGF-B and downregulation of interleukin-22 (IL-22) among DN patients were significantly associated with the progression of DN. Thus, we hypothesized that a combination of a VEGF-B antibody and IL-22 could protect against DN not only by regulating glycolipid metabolism but also by reducing the accumulation of inflammation and ROS. To meet these challenges, a novel anti-VEGFB/IL22 fusion protein was developed, and its therapeutic effects on DN were further studied. We found that the anti-VEGFB/IL22 fusion protein reduced renal lipid accumulation by inhibiting the expression of fatty acid transport proteins and ameliorated inflammatory responses
