Back to Search
Start Over
Macrophage-stimulating protein attenuates gentamicin-induced inflammation and apoptosis in human renal proximal tubular epithelial cells.
- Source :
-
Biochemical and biophysical research communications [Biochem Biophys Res Commun] 2013 May 10; Vol. 434 (3), pp. 527-33. Date of Electronic Publication: 2013 Apr 10. - Publication Year :
- 2013
-
Abstract
- The present study aimed to investigate whether macrophage-stimulating protein (MSP) treatment attenuates renal apoptosis and inflammation in gentamicin (GM)-induced tubule injury and its underlying molecular mechanisms. To examine changes in MSP and its receptor, recepteur d'origine nantais (RON) in GM-induced nephropathy, rats were injected with GM for 7 days. Human renal proximal tubular epithelial (HK-2) cells were incubated with GM for 24h in the presence of different concentrations of MSP and cell viability was measured by MTT assay. Apoptosis was determined by flow cytometry of cells stained with fluorescein isothiocyanate-conjugated annexin V protein and propidium iodide. Expression of Bcl-2, Bax, caspase-3, cyclooxygenase (COX)-2, inducible nitric oxide synthase (iNOS), nuclear factor-kappa B (NF-κB), IκB-α, and mitogen-activated protein kinases (MAPKs) was analyzed by semiquantitative immunoblotting. MSP and RON expression was significantly greater in GM-treated rats, than in untreated controls. GM-treatment reduced HK-2 cell viability, an effect that was counteracted by MSP. Flow cytometry and DAPI staining revealed GM-induced apoptosis was prevented by MSP. GM reduced expression of anti-apoptotic protein Bcl-2 and induced expression of Bax and cleaved caspase 3; these effects and GM-induced expression of COX-2 and iNOS were also attenuated by MSP. GM caused MSP-reversible induction of phospho-ERK, phospho-JNK, and phospho-p38. GM induced NF-κB activation and degradation of IκB-α; the increase in nuclear NF-κB was blocked by inhibitors of ERK, JNK, p-38, or MSP pretreatment. These findings suggest that MSP attenuates GM-induced inflammation and apoptosis by inhibition of the MAPKs/NF-κB signaling pathways.<br /> (Copyright © 2013 Elsevier Inc. All rights reserved.)
- Subjects :
- Cell Line
Epithelial Cells drug effects
Epithelial Cells enzymology
Epithelial Cells metabolism
Flow Cytometry
Humans
Inflammation physiopathology
Kidney Tubules, Proximal cytology
Kidney Tubules, Proximal metabolism
Apoptosis drug effects
Gentamicins pharmacology
Hepatocyte Growth Factor physiology
Inflammation chemically induced
Kidney Tubules, Proximal drug effects
Proto-Oncogene Proteins physiology
Subjects
Details
- Language :
- English
- ISSN :
- 1090-2104
- Volume :
- 434
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- Biochemical and biophysical research communications
- Publication Type :
- Academic Journal
- Accession number :
- 23583394
- Full Text :
- https://doi.org/10.1016/j.bbrc.2013.03.108