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VEGF-B antibody and interleukin-22 fusion protein ameliorates diabetic nephropathy through inhibiting lipid accumulation and inflammatory responses

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 ameliorat...

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Autores principales: Shen, Yilan, Chen, Wei, Han, Lei, Bian, Qi, Fan, Jiajun, Cao, Zhonglian, Jin, Xin, Ding, Tao, Xian, Zongshu, Guo, Zhiyong, Zhang, Wei, Ju, Dianwen, Mei, Xiaobin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7838033/
https://www.ncbi.nlm.nih.gov/pubmed/33532185
http://dx.doi.org/10.1016/j.apsb.2020.07.002
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author Shen, Yilan
Chen, Wei
Han, Lei
Bian, Qi
Fan, Jiajun
Cao, Zhonglian
Jin, Xin
Ding, Tao
Xian, Zongshu
Guo, Zhiyong
Zhang, Wei
Ju, Dianwen
Mei, Xiaobin
author_facet Shen, Yilan
Chen, Wei
Han, Lei
Bian, Qi
Fan, Jiajun
Cao, Zhonglian
Jin, Xin
Ding, Tao
Xian, Zongshu
Guo, Zhiyong
Zhang, Wei
Ju, Dianwen
Mei, Xiaobin
author_sort Shen, Yilan
collection PubMed
description 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 via the inhibition of renal oxidative stress and mitochondrial dysfunction. Moreover, the fusion protein could also improve diabetic kidney disease by increasing insulin sensitivity. Collectively, our findings indicate that the bifunctional VEGF-B antibody and IL-22 fusion protein could improve the progression of DN, which highlighted a novel therapeutic approach to DN.
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spelling pubmed-78380332021-02-01 VEGF-B antibody and interleukin-22 fusion protein ameliorates diabetic nephropathy through inhibiting lipid accumulation and inflammatory responses Shen, Yilan Chen, Wei Han, Lei Bian, Qi Fan, Jiajun Cao, Zhonglian Jin, Xin Ding, Tao Xian, Zongshu Guo, Zhiyong Zhang, Wei Ju, Dianwen Mei, Xiaobin Acta Pharm Sin B Original Article 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 via the inhibition of renal oxidative stress and mitochondrial dysfunction. Moreover, the fusion protein could also improve diabetic kidney disease by increasing insulin sensitivity. Collectively, our findings indicate that the bifunctional VEGF-B antibody and IL-22 fusion protein could improve the progression of DN, which highlighted a novel therapeutic approach to DN. Elsevier 2021-01 2020-07-13 /pmc/articles/PMC7838033/ /pubmed/33532185 http://dx.doi.org/10.1016/j.apsb.2020.07.002 Text en © 2021 Chinese Pharmaceutical Association and Institute of Materia Medica, Chinese Academy of Medical Sciences. Production and hosting by Elsevier B.V. http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Original Article
Shen, Yilan
Chen, Wei
Han, Lei
Bian, Qi
Fan, Jiajun
Cao, Zhonglian
Jin, Xin
Ding, Tao
Xian, Zongshu
Guo, Zhiyong
Zhang, Wei
Ju, Dianwen
Mei, Xiaobin
VEGF-B antibody and interleukin-22 fusion protein ameliorates diabetic nephropathy through inhibiting lipid accumulation and inflammatory responses
title VEGF-B antibody and interleukin-22 fusion protein ameliorates diabetic nephropathy through inhibiting lipid accumulation and inflammatory responses
title_full VEGF-B antibody and interleukin-22 fusion protein ameliorates diabetic nephropathy through inhibiting lipid accumulation and inflammatory responses
title_fullStr VEGF-B antibody and interleukin-22 fusion protein ameliorates diabetic nephropathy through inhibiting lipid accumulation and inflammatory responses
title_full_unstemmed VEGF-B antibody and interleukin-22 fusion protein ameliorates diabetic nephropathy through inhibiting lipid accumulation and inflammatory responses
title_short VEGF-B antibody and interleukin-22 fusion protein ameliorates diabetic nephropathy through inhibiting lipid accumulation and inflammatory responses
title_sort vegf-b antibody and interleukin-22 fusion protein ameliorates diabetic nephropathy through inhibiting lipid accumulation and inflammatory responses
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7838033/
https://www.ncbi.nlm.nih.gov/pubmed/33532185
http://dx.doi.org/10.1016/j.apsb.2020.07.002
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