Cargando…

Paeoniflorin directly binds to TNFR1 to regulate podocyte necroptosis in diabetic kidney disease

Necroptosis was elevated in both tubulointerstitial and glomerular renal tissue in patients with diabetic kidney disease (DKD), and was most pronounced on glomerulus in the stage with macroalbuminuria. This study further explored whether paeoniflorin (PF) could affect podocyte necroptosis to protect...

Descripción completa

Detalles Bibliográficos
Autores principales: Wang, Xian, Liu, Xue-qi, Jiang, Ling, Huang, Yue-bo, Zeng, Han-xu, Zhu, Qi-jin, Qi, Xiang-ming, Wu, Yong-gui
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9486100/
https://www.ncbi.nlm.nih.gov/pubmed/36147345
http://dx.doi.org/10.3389/fphar.2022.966645
_version_ 1784792203545018368
author Wang, Xian
Liu, Xue-qi
Jiang, Ling
Huang, Yue-bo
Zeng, Han-xu
Zhu, Qi-jin
Qi, Xiang-ming
Wu, Yong-gui
author_facet Wang, Xian
Liu, Xue-qi
Jiang, Ling
Huang, Yue-bo
Zeng, Han-xu
Zhu, Qi-jin
Qi, Xiang-ming
Wu, Yong-gui
author_sort Wang, Xian
collection PubMed
description Necroptosis was elevated in both tubulointerstitial and glomerular renal tissue in patients with diabetic kidney disease (DKD), and was most pronounced on glomerulus in the stage with macroalbuminuria. This study further explored whether paeoniflorin (PF) could affect podocyte necroptosis to protect kidney injure in vivo and in vitro. Our study firstly verified that there are obvious necroptosis-related changes in the glomeruli of DKD through bioinformatics analysis combined with clinicopathological data. STZ-induced mouse diabetes model and high-glucose induced podocyte injury model were used to evaluate the renoprotection, podocyte injury protection and necroptosis regulation of PF in DKD. Subsequently, the target protein-TNFR1 that PF acted on podocytes was found by computer target prediction, and then molecular docking and Surface plasmon resonance (SPR) experiments were performed to verify that PF had the ability to directly bind to TNFR1 protein. Finally, knockdown of TNFR1 on podocytes in vitro verified that PF mainly regulated the programmed necrosis of podocytes induced by high glucose through TNFR1. In conclusion, PF can directly bind and promote the degradation of TNFR1 in podocytes and then regulate the RIPK1/RIPK3 signaling pathway to affect necroptosis, thus preventing podocyte injury in DKD. Thus, TNFR1 may be used as a new potential target to treat DKD.
format Online
Article
Text
id pubmed-9486100
institution National Center for Biotechnology Information
language English
publishDate 2022
publisher Frontiers Media S.A.
record_format MEDLINE/PubMed
spelling pubmed-94861002022-09-21 Paeoniflorin directly binds to TNFR1 to regulate podocyte necroptosis in diabetic kidney disease Wang, Xian Liu, Xue-qi Jiang, Ling Huang, Yue-bo Zeng, Han-xu Zhu, Qi-jin Qi, Xiang-ming Wu, Yong-gui Front Pharmacol Pharmacology Necroptosis was elevated in both tubulointerstitial and glomerular renal tissue in patients with diabetic kidney disease (DKD), and was most pronounced on glomerulus in the stage with macroalbuminuria. This study further explored whether paeoniflorin (PF) could affect podocyte necroptosis to protect kidney injure in vivo and in vitro. Our study firstly verified that there are obvious necroptosis-related changes in the glomeruli of DKD through bioinformatics analysis combined with clinicopathological data. STZ-induced mouse diabetes model and high-glucose induced podocyte injury model were used to evaluate the renoprotection, podocyte injury protection and necroptosis regulation of PF in DKD. Subsequently, the target protein-TNFR1 that PF acted on podocytes was found by computer target prediction, and then molecular docking and Surface plasmon resonance (SPR) experiments were performed to verify that PF had the ability to directly bind to TNFR1 protein. Finally, knockdown of TNFR1 on podocytes in vitro verified that PF mainly regulated the programmed necrosis of podocytes induced by high glucose through TNFR1. In conclusion, PF can directly bind and promote the degradation of TNFR1 in podocytes and then regulate the RIPK1/RIPK3 signaling pathway to affect necroptosis, thus preventing podocyte injury in DKD. Thus, TNFR1 may be used as a new potential target to treat DKD. Frontiers Media S.A. 2022-09-06 /pmc/articles/PMC9486100/ /pubmed/36147345 http://dx.doi.org/10.3389/fphar.2022.966645 Text en Copyright © 2022 Wang, Liu, Jiang, Huang, Zeng, Zhu, Qi and Wu. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Pharmacology
Wang, Xian
Liu, Xue-qi
Jiang, Ling
Huang, Yue-bo
Zeng, Han-xu
Zhu, Qi-jin
Qi, Xiang-ming
Wu, Yong-gui
Paeoniflorin directly binds to TNFR1 to regulate podocyte necroptosis in diabetic kidney disease
title Paeoniflorin directly binds to TNFR1 to regulate podocyte necroptosis in diabetic kidney disease
title_full Paeoniflorin directly binds to TNFR1 to regulate podocyte necroptosis in diabetic kidney disease
title_fullStr Paeoniflorin directly binds to TNFR1 to regulate podocyte necroptosis in diabetic kidney disease
title_full_unstemmed Paeoniflorin directly binds to TNFR1 to regulate podocyte necroptosis in diabetic kidney disease
title_short Paeoniflorin directly binds to TNFR1 to regulate podocyte necroptosis in diabetic kidney disease
title_sort paeoniflorin directly binds to tnfr1 to regulate podocyte necroptosis in diabetic kidney disease
topic Pharmacology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9486100/
https://www.ncbi.nlm.nih.gov/pubmed/36147345
http://dx.doi.org/10.3389/fphar.2022.966645
work_keys_str_mv AT wangxian paeoniflorindirectlybindstotnfr1toregulatepodocytenecroptosisindiabetickidneydisease
AT liuxueqi paeoniflorindirectlybindstotnfr1toregulatepodocytenecroptosisindiabetickidneydisease
AT jiangling paeoniflorindirectlybindstotnfr1toregulatepodocytenecroptosisindiabetickidneydisease
AT huangyuebo paeoniflorindirectlybindstotnfr1toregulatepodocytenecroptosisindiabetickidneydisease
AT zenghanxu paeoniflorindirectlybindstotnfr1toregulatepodocytenecroptosisindiabetickidneydisease
AT zhuqijin paeoniflorindirectlybindstotnfr1toregulatepodocytenecroptosisindiabetickidneydisease
AT qixiangming paeoniflorindirectlybindstotnfr1toregulatepodocytenecroptosisindiabetickidneydisease
AT wuyonggui paeoniflorindirectlybindstotnfr1toregulatepodocytenecroptosisindiabetickidneydisease