Cargando…

A Cell-Penetrating Peptide That Blocks Toll-Like Receptor Signaling Protects Kidneys against Ischemia-Reperfusion Injury

Renal ischemia-reperfusion injury (IRI) is involved in the majority of clinical conditions that manifest as renal function deterioration; however, specific treatment for this type of injury is still far from clinical use. Since Toll-like receptor (TLR)-mediated signaling is a key mediator of IRI, we...

Descripción completa

Detalles Bibliográficos
Autores principales: Jung, Su Woong, Seo, Jung-Woo, Park, Seon Hwa, Kim, Yang Gyun, Moon, Ju-Young, Choi, Sangdun, Lee, Sang-Ho
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7915942/
https://www.ncbi.nlm.nih.gov/pubmed/33562802
http://dx.doi.org/10.3390/ijms22041627
_version_ 1783657364754268160
author Jung, Su Woong
Seo, Jung-Woo
Park, Seon Hwa
Kim, Yang Gyun
Moon, Ju-Young
Choi, Sangdun
Lee, Sang-Ho
author_facet Jung, Su Woong
Seo, Jung-Woo
Park, Seon Hwa
Kim, Yang Gyun
Moon, Ju-Young
Choi, Sangdun
Lee, Sang-Ho
author_sort Jung, Su Woong
collection PubMed
description Renal ischemia-reperfusion injury (IRI) is involved in the majority of clinical conditions that manifest as renal function deterioration; however, specific treatment for this type of injury is still far from clinical use. Since Toll-like receptor (TLR)-mediated signaling is a key mediator of IRI, we examined the effect of a multiple-TLR-blocking peptide named TLR-inhibitory peptide 1 (TIP1), which exerts the strongest action on TLR4, on renal IRI. We subjected C57BL/6 mice to 23 min of renal pedicle clamping preceded by intraperitoneal injection with a vehicle or TIP1. Sham control mice underwent flank incision only. Mouse kidneys were harvested after 24 h of reperfusion for histology, western blot, RT-PCR, and flow cytometry analysis. Pretreatment with TIP1 lowered the magnitude of elevated plasma creatinine levels and attenuated tubular injury. TIP1 treatment also reduced mRNA expression of inflammatory cytokines and decreased apoptotic cells and oxidative stress in post-ischemic kidneys. In kidneys pretreated with TIP1, the infiltration of macrophages and T helper 17 cells was less abundant than those in the IRI only group. These results suggest that TIP1 has a potential beneficial effect in attenuating the degree of kidney damage induced by IRI.
format Online
Article
Text
id pubmed-7915942
institution National Center for Biotechnology Information
language English
publishDate 2021
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-79159422021-03-01 A Cell-Penetrating Peptide That Blocks Toll-Like Receptor Signaling Protects Kidneys against Ischemia-Reperfusion Injury Jung, Su Woong Seo, Jung-Woo Park, Seon Hwa Kim, Yang Gyun Moon, Ju-Young Choi, Sangdun Lee, Sang-Ho Int J Mol Sci Article Renal ischemia-reperfusion injury (IRI) is involved in the majority of clinical conditions that manifest as renal function deterioration; however, specific treatment for this type of injury is still far from clinical use. Since Toll-like receptor (TLR)-mediated signaling is a key mediator of IRI, we examined the effect of a multiple-TLR-blocking peptide named TLR-inhibitory peptide 1 (TIP1), which exerts the strongest action on TLR4, on renal IRI. We subjected C57BL/6 mice to 23 min of renal pedicle clamping preceded by intraperitoneal injection with a vehicle or TIP1. Sham control mice underwent flank incision only. Mouse kidneys were harvested after 24 h of reperfusion for histology, western blot, RT-PCR, and flow cytometry analysis. Pretreatment with TIP1 lowered the magnitude of elevated plasma creatinine levels and attenuated tubular injury. TIP1 treatment also reduced mRNA expression of inflammatory cytokines and decreased apoptotic cells and oxidative stress in post-ischemic kidneys. In kidneys pretreated with TIP1, the infiltration of macrophages and T helper 17 cells was less abundant than those in the IRI only group. These results suggest that TIP1 has a potential beneficial effect in attenuating the degree of kidney damage induced by IRI. MDPI 2021-02-05 /pmc/articles/PMC7915942/ /pubmed/33562802 http://dx.doi.org/10.3390/ijms22041627 Text en © 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Jung, Su Woong
Seo, Jung-Woo
Park, Seon Hwa
Kim, Yang Gyun
Moon, Ju-Young
Choi, Sangdun
Lee, Sang-Ho
A Cell-Penetrating Peptide That Blocks Toll-Like Receptor Signaling Protects Kidneys against Ischemia-Reperfusion Injury
title A Cell-Penetrating Peptide That Blocks Toll-Like Receptor Signaling Protects Kidneys against Ischemia-Reperfusion Injury
title_full A Cell-Penetrating Peptide That Blocks Toll-Like Receptor Signaling Protects Kidneys against Ischemia-Reperfusion Injury
title_fullStr A Cell-Penetrating Peptide That Blocks Toll-Like Receptor Signaling Protects Kidneys against Ischemia-Reperfusion Injury
title_full_unstemmed A Cell-Penetrating Peptide That Blocks Toll-Like Receptor Signaling Protects Kidneys against Ischemia-Reperfusion Injury
title_short A Cell-Penetrating Peptide That Blocks Toll-Like Receptor Signaling Protects Kidneys against Ischemia-Reperfusion Injury
title_sort cell-penetrating peptide that blocks toll-like receptor signaling protects kidneys against ischemia-reperfusion injury
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7915942/
https://www.ncbi.nlm.nih.gov/pubmed/33562802
http://dx.doi.org/10.3390/ijms22041627
work_keys_str_mv AT jungsuwoong acellpenetratingpeptidethatblockstolllikereceptorsignalingprotectskidneysagainstischemiareperfusioninjury
AT seojungwoo acellpenetratingpeptidethatblockstolllikereceptorsignalingprotectskidneysagainstischemiareperfusioninjury
AT parkseonhwa acellpenetratingpeptidethatblockstolllikereceptorsignalingprotectskidneysagainstischemiareperfusioninjury
AT kimyanggyun acellpenetratingpeptidethatblockstolllikereceptorsignalingprotectskidneysagainstischemiareperfusioninjury
AT moonjuyoung acellpenetratingpeptidethatblockstolllikereceptorsignalingprotectskidneysagainstischemiareperfusioninjury
AT choisangdun acellpenetratingpeptidethatblockstolllikereceptorsignalingprotectskidneysagainstischemiareperfusioninjury
AT leesangho acellpenetratingpeptidethatblockstolllikereceptorsignalingprotectskidneysagainstischemiareperfusioninjury
AT jungsuwoong cellpenetratingpeptidethatblockstolllikereceptorsignalingprotectskidneysagainstischemiareperfusioninjury
AT seojungwoo cellpenetratingpeptidethatblockstolllikereceptorsignalingprotectskidneysagainstischemiareperfusioninjury
AT parkseonhwa cellpenetratingpeptidethatblockstolllikereceptorsignalingprotectskidneysagainstischemiareperfusioninjury
AT kimyanggyun cellpenetratingpeptidethatblockstolllikereceptorsignalingprotectskidneysagainstischemiareperfusioninjury
AT moonjuyoung cellpenetratingpeptidethatblockstolllikereceptorsignalingprotectskidneysagainstischemiareperfusioninjury
AT choisangdun cellpenetratingpeptidethatblockstolllikereceptorsignalingprotectskidneysagainstischemiareperfusioninjury
AT leesangho cellpenetratingpeptidethatblockstolllikereceptorsignalingprotectskidneysagainstischemiareperfusioninjury