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Inhibition of Toll-Like Receptor 4 Signaling Mitigates Microvascular Loss but Not Fibrosis in a Model of Ischemic Acute Kidney Injury
Inhibition of Toll-Like Receptor 4 Signaling Mitigates Microvascular Loss but Not Fibrosis in a Model of Ischemic Acute Kidney Injury
- Source :
- International Journal of Molecular Sciences, Vol 17, Iss 5, p 647 (2016), International Journal of Molecular Sciences; Volume 17; Issue 5; Pages: 647, International Journal of Molecular Sciences
- Publication Year :
- 2016
- Publisher :
- MDPI AG, 2016.
-
Abstract
- The development of chronic kidney disease (CKD) following an episode of acute kidney injury (AKI) is an increasingly recognized clinical problem. Inhibition of toll-like receptor 4 (TLR4) protects renal function in animal models of AKI and has become a viable therapeutic strategy in AKI. However, the impact of TLR4 inhibition on the chronic sequelae of AKI is unknown. Consequently, we examined the chronic effects of TLR4 inhibition in a model of ischemic AKI. Mice with a TLR4-deletion on a C57BL/6 background and wild-type (WT) background control mice (C57BL/6) were subjected to bilateral renal artery clamping for 19 min and reperfusion for up to 6 weeks. Despite the acute protective effect of TLR4 inhibition on renal function (serum creatinine 1.6 ± 0.4 mg/dL TLR4-deletion vs. 2.8 ± 0.3 mg/dL·WT) and rates of tubular apoptosis following ischemic AKI, we found no difference in neutrophil or macrophage infiltration. Furthermore, we observed significant protection from microvascular rarefaction at six weeks following injury with TLR4-deletion, but this did not alter development of fibrosis. In conclusion, we validate the acute protective effect of TLR4 signal inhibition in AKI but demonstrate that this protective effect does not mitigate the sequential fibrogenic response in this model of ischemic AKI.
- Subjects :
- Male
0301 basic medicine
toll-like receptor 4
030232 urology & nephrology
Apoptosis
Kidney
urologic and male genital diseases
ischemia-reperfusion
lcsh:Chemistry
Mice
chemistry.chemical_compound
0302 clinical medicine
Fibrosis
lcsh:QH301-705.5
Spectroscopy
Mice, Knockout
Acute kidney injury
General Medicine
acute kidney injury
fibrosis
female genital diseases and pregnancy complications
3. Good health
Computer Science Applications
medicine.anatomical_structure
Creatinine
Signal Transduction
medicine.medical_specialty
Urology
Renal function
Article
Catalysis
Inorganic Chemistry
03 medical and health sciences
medicine.artery
medicine
Animals
Physical and Theoretical Chemistry
Renal artery
Molecular Biology
business.industry
urogenital system
Organic Chemistry
medicine.disease
Mice, Inbred C57BL
Disease Models, Animal
030104 developmental biology
chemistry
lcsh:Biology (General)
lcsh:QD1-999
Microvessels
Immunology
TLR4
business
Kidney disease
Subjects
Details
- Language :
- English
- ISSN :
- 14220067
- Volume :
- 17
- Issue :
- 5
- Database :
- OpenAIRE
- Journal :
- International Journal of Molecular Sciences
- Accession number :
- edsair.doi.dedup.....408798a017972bf39c71bff7a6a8593a