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TLR2 mediates renal apoptosis in neonatal mice subjected experimentally to obstructive nephropathy
Urinary tract obstruction during renal development leads to inflammation, tubular apoptosis, and interstitial fibrosis. Toll like receptors (TLRs) expressed on leukocytes, myofibroblasts and renal cells play a central role in acute inflammation. TLR2 is activated by endogenous danger signals in the...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10684073/ https://www.ncbi.nlm.nih.gov/pubmed/38015955 http://dx.doi.org/10.1371/journal.pone.0294142 |
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author | Wyczanska, Maja Rohling, Jana Keller, Ursula Benz, Marcus R. Kirschning, Carsten Lange-Sperandio, Bärbel |
author_facet | Wyczanska, Maja Rohling, Jana Keller, Ursula Benz, Marcus R. Kirschning, Carsten Lange-Sperandio, Bärbel |
author_sort | Wyczanska, Maja |
collection | PubMed |
description | Urinary tract obstruction during renal development leads to inflammation, tubular apoptosis, and interstitial fibrosis. Toll like receptors (TLRs) expressed on leukocytes, myofibroblasts and renal cells play a central role in acute inflammation. TLR2 is activated by endogenous danger signals in the kidney; its contribution to renal injury in early life is still a controversial topic. We analyzed TLR2 for a potential role in the neonatal mouse model of congenital obstructive nephropathy. Inborn obstructive nephropathies are a leading cause of end-stage kidney disease in children. Thus, newborn Tlr2(-/-) and wild type (WT) C57BL/6 mice were subjected to complete unilateral ureteral obstruction (UUO) or sham-operation on the 2(nd) day of life. The neonatal kidneys were harvested and analyzed at days 7 and 14 of life. Relative expression levels of TLR2, caspase-8, Bcl-2, Bax, GSDMD, GSDME, HMGB1, TNF, galectin-3, α-SMA, MMP-2, and TGF-β proteins were quantified semi-quantitatively by immunoblot analyses. Tubular apoptosis, proliferation, macrophage- and T-cell infiltration, tubular atrophy, and interstitial fibrosis were analyzed immunohistochemically. Neonatal Tlr2(-/-) mice kidneys exhibited less tubular and interstitial apoptosis as compared to those of WT C57BL/6 mice after UUO. UUO induced neonatally did trigger pyroptosis in kidneys, however to similar degrees in Tlr2(-/-) and WT mice. Also, tubular atrophy, interstitial fibrosis, tubular proliferation, as well as macrophage and T-cell infiltration were unremarkable. We conclude that while TLR2 mediates apoptosis in the kidneys of neonatal mice subjected to UUO, leukocyte recruitment, interstitial fibrosis, and consequent neonatal obstructive nephropathy might lack a TLR2 involvement. |
format | Online Article Text |
id | pubmed-10684073 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-106840732023-11-30 TLR2 mediates renal apoptosis in neonatal mice subjected experimentally to obstructive nephropathy Wyczanska, Maja Rohling, Jana Keller, Ursula Benz, Marcus R. Kirschning, Carsten Lange-Sperandio, Bärbel PLoS One Research Article Urinary tract obstruction during renal development leads to inflammation, tubular apoptosis, and interstitial fibrosis. Toll like receptors (TLRs) expressed on leukocytes, myofibroblasts and renal cells play a central role in acute inflammation. TLR2 is activated by endogenous danger signals in the kidney; its contribution to renal injury in early life is still a controversial topic. We analyzed TLR2 for a potential role in the neonatal mouse model of congenital obstructive nephropathy. Inborn obstructive nephropathies are a leading cause of end-stage kidney disease in children. Thus, newborn Tlr2(-/-) and wild type (WT) C57BL/6 mice were subjected to complete unilateral ureteral obstruction (UUO) or sham-operation on the 2(nd) day of life. The neonatal kidneys were harvested and analyzed at days 7 and 14 of life. Relative expression levels of TLR2, caspase-8, Bcl-2, Bax, GSDMD, GSDME, HMGB1, TNF, galectin-3, α-SMA, MMP-2, and TGF-β proteins were quantified semi-quantitatively by immunoblot analyses. Tubular apoptosis, proliferation, macrophage- and T-cell infiltration, tubular atrophy, and interstitial fibrosis were analyzed immunohistochemically. Neonatal Tlr2(-/-) mice kidneys exhibited less tubular and interstitial apoptosis as compared to those of WT C57BL/6 mice after UUO. UUO induced neonatally did trigger pyroptosis in kidneys, however to similar degrees in Tlr2(-/-) and WT mice. Also, tubular atrophy, interstitial fibrosis, tubular proliferation, as well as macrophage and T-cell infiltration were unremarkable. We conclude that while TLR2 mediates apoptosis in the kidneys of neonatal mice subjected to UUO, leukocyte recruitment, interstitial fibrosis, and consequent neonatal obstructive nephropathy might lack a TLR2 involvement. Public Library of Science 2023-11-28 /pmc/articles/PMC10684073/ /pubmed/38015955 http://dx.doi.org/10.1371/journal.pone.0294142 Text en © 2023 Wyczanska et al https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Article Wyczanska, Maja Rohling, Jana Keller, Ursula Benz, Marcus R. Kirschning, Carsten Lange-Sperandio, Bärbel TLR2 mediates renal apoptosis in neonatal mice subjected experimentally to obstructive nephropathy |
title | TLR2 mediates renal apoptosis in neonatal mice subjected experimentally to obstructive nephropathy |
title_full | TLR2 mediates renal apoptosis in neonatal mice subjected experimentally to obstructive nephropathy |
title_fullStr | TLR2 mediates renal apoptosis in neonatal mice subjected experimentally to obstructive nephropathy |
title_full_unstemmed | TLR2 mediates renal apoptosis in neonatal mice subjected experimentally to obstructive nephropathy |
title_short | TLR2 mediates renal apoptosis in neonatal mice subjected experimentally to obstructive nephropathy |
title_sort | tlr2 mediates renal apoptosis in neonatal mice subjected experimentally to obstructive nephropathy |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10684073/ https://www.ncbi.nlm.nih.gov/pubmed/38015955 http://dx.doi.org/10.1371/journal.pone.0294142 |
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