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...

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Bibliographic Details
Published in:PloS one 2023-11, Vol.18 (11), p.e0294142-e0294142
Main Authors: Wyczanska, Maja, Rohling, Jana, Keller, Ursula, Benz, Marcus R, Kirschning, Carsten, Lange-Sperandio, Bärbel
Format: Article
Language:English
Subjects:
Analysis
Apoptosis
Biology and Life Sciences
Children
Chromosomal proteins
Chronic kidney failure
Complications and side effects
Development and progression
Diseases
Health aspects
Infants (Newborn)
Inflammation
Kidney diseases
Macrophages
Mediation
Medicine and Health Sciences
Methylene blue
Research and Analysis Methods
T cells
TLR2
Transforming growth factors
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Summary: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.sup.-/- and wild type (WT) C57BL/6 mice were subjected to complete unilateral ureteral obstruction (UUO) or sham-operation on the 2.sup.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, [alpha]-SMA, MMP-2, and TGF-[beta] 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.sup.-/- 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.sup.-/- 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.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0294142