Long-Term Protection of CHBP Against Combinational Renal Injury Induced by Both Ischemia-Reperfusion and Cyclosporine A in Mice.
Animals
Apoptosis
/ drug effects
Caspase 3
/ genetics
Caspase Inhibitors
/ pharmacology
Cell Line
Cyclosporine
/ pharmacology
Disease Models, Animal
Erythropoietin
/ chemistry
Kidney
/ blood supply
Macrophages
/ drug effects
Male
Mice
Mice, Inbred BALB C
Peptide Fragments
/ chemistry
Peptides, Cyclic
/ chemistry
RNA, Messenger
/ genetics
RNA, Small Interfering
/ genetics
Reperfusion Injury
/ pathology
CASP-3
apoptosis
cyclic helix B peptide
cyclosporine A
ischemia–reperfusion injury
Journal
Frontiers in immunology
ISSN: 1664-3224
Titre abrégé: Front Immunol
Pays: Switzerland
ID NLM: 101560960
Informations de publication
Date de publication:
2021
2021
Historique:
received:
20
04
2021
accepted:
25
06
2021
entrez:
12
8
2021
pubmed:
13
8
2021
medline:
15
12
2021
Statut:
epublish
Résumé
Renal ischemia-reperfusion (IR) injury and cyclosporine A (CsA) nephrotoxicity affect allograft function and survival. The prolonged effects and underlying mechanisms of erythropoietin derived cyclic helix B peptide (CHBP) and/or caspase-3 small interfering RNA (CASP-3siRNA) were investigated in mouse kidneys, as well as kidney epithelial cells (TCMK-1), subjected to transplant-related injuries. Bilateral renal pedicles were clamped for 30 min followed by reperfusion for 2 and 8 weeks, with/without 35 mg/kg CsA gavage daily and/or 24 nmol/kg CHBP intraperitoneal injection every 3 days. The ratio of urinary albumin to creatinine was raised by IR injury, further increased by CsA and lowered by CHBP at 2, 4, 6 and 8 weeks, whereas the level of SCr was not significantly affected. Similar change trends were revealed in tubulointerstitial damage and fibrosis, HMGB1 and active CASP-3 protein. Increased apoptotic cells in IR kidneys were decreased by CsA and CHBP at 2 and/or 8 weeks. p70 S6 kinase and mTOR were reduced by CsA with/without CHBP at 2 weeks, so were S6 ribosomal protein and GSK-3β at 8 weeks, with reduced CASP-3 at both time points. CASP-3 was further decreased by CHBP in IR or IR + CsA kidneys at 2 or 8 weeks. Furthermore, in TCMK-1 cells CsA induced apoptosis was decreased by CHBP and/or CASP-3siRNA treatment. Taken together, CHBP predominantly protects kidneys against IR injury at 2 weeks and/or CsA nephrotoxicity at 8 weeks, with different underlying mechanisms. Urinary albumin/creatinine is a good biomarker in monitoring the progression of transplant-related injuries. CsA divergently affects apoptosis in kidneys and cultured kidney epithelial cells, in which CHBP and/or CASP-3siRNA reduces inflammation and apoptosis.
Identifiants
pubmed: 34381450
doi: 10.3389/fimmu.2021.697751
pmc: PMC8350137
doi:
Substances chimiques
Caspase Inhibitors
0
Epo protein, mouse
0
Peptide Fragments
0
Peptides, Cyclic
0
RNA, Messenger
0
RNA, Small Interfering
0
glutaminyl-glutamyl-glutaminyl-leucyl-glutamyl-arginyl-alanyl-leucyl-asparagyl-seryl-serine
0
Erythropoietin
11096-26-7
Cyclosporine
83HN0GTJ6D
Casp3 protein, mouse
EC 3.4.22.-
Caspase 3
EC 3.4.22.-
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
697751Informations de copyright
Copyright © 2021 Zhang, Wu, Wang, Liu, Zhang, Yang, Liu, Wu, Zhu, Nicholson, Fan and Yang.
Déclaration de conflit d'intérêts
The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
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