Cargando…
Accelerated Glomerular Cell Senescence in Experimental Lupus Nephritis
BACKGROUND: The aim of this study was to determine whether senescence in renal glomeruli is involved in lupus nephritis (LN); the expression of senescence-associated β-galactosidase (SA-β-Gal) and its association with glomerular lesions were investigated in a mouse model of LN. MATERIAL/METHODS: Eig...
Autores principales: | , , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
International Scientific Literature, Inc.
2018
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6180956/ https://www.ncbi.nlm.nih.gov/pubmed/30265659 http://dx.doi.org/10.12659/MSM.909353 |
_version_ | 1783362319203434496 |
---|---|
author | Yang, Chen Xue, Jing An, Ning Huang, Xi-jie Wu, Zhi-hong Ye, Lin Li, Zhi-hang Wang, Shu-jun Pan, Qing-jun Liang, Dong Liu, Hua-feng |
author_facet | Yang, Chen Xue, Jing An, Ning Huang, Xi-jie Wu, Zhi-hong Ye, Lin Li, Zhi-hang Wang, Shu-jun Pan, Qing-jun Liang, Dong Liu, Hua-feng |
author_sort | Yang, Chen |
collection | PubMed |
description | BACKGROUND: The aim of this study was to determine whether senescence in renal glomeruli is involved in lupus nephritis (LN); the expression of senescence-associated β-galactosidase (SA-β-Gal) and its association with glomerular lesions were investigated in a mouse model of LN. MATERIAL/METHODS: Eighteen MRL/lpr mice with severe proteinuria were randomly divided into 2 equal groups and intraperitoneally injected with dexamethasone (DEX) or saline; 4 age-matched mice with mild proteinuria served as controls. Serum creatinine and urinary protein levels were analyzed, and kidney histological changes were observed by periodic acid–Schiff and Sirius Red staining. SA-β-Gal was detected via histochemistry. Glomerular expression of collagen IV, α-SMA, and nephrin was analyzed by immunohistochemistry, and glomerular complement C3 deposition was tested by immunofluorescence. The relationships between SA-β-Gal expression and renal function or glomerular lesion markers were determined by Spearman’s correlation analysis. RESULTS: Mice with severe proteinuria exhibited glomerular segmental sclerosis and endothelial cell proliferation. DEX administration suppressed these lesions but had no significant effect on 24-hour urinary protein levels. The elevated glomerular expression of SA-β-Gal in proteinuric mice was attenuated by DEX treatment. In addition, DEX treatment markedly downregulated glomerular C3 deposition and collagen IV and α-SMA expression, while significantly increasing nephrin expression. Furthermore, SA-β-Gal expression was positively correlated with urinary protein levels and expression of α-SMA. CONCLUSIONS: Accelerated senescence of glomerular cells may contribute to glomerular injury in LN. |
format | Online Article Text |
id | pubmed-6180956 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | International Scientific Literature, Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-61809562018-10-15 Accelerated Glomerular Cell Senescence in Experimental Lupus Nephritis Yang, Chen Xue, Jing An, Ning Huang, Xi-jie Wu, Zhi-hong Ye, Lin Li, Zhi-hang Wang, Shu-jun Pan, Qing-jun Liang, Dong Liu, Hua-feng Med Sci Monit Animal Study BACKGROUND: The aim of this study was to determine whether senescence in renal glomeruli is involved in lupus nephritis (LN); the expression of senescence-associated β-galactosidase (SA-β-Gal) and its association with glomerular lesions were investigated in a mouse model of LN. MATERIAL/METHODS: Eighteen MRL/lpr mice with severe proteinuria were randomly divided into 2 equal groups and intraperitoneally injected with dexamethasone (DEX) or saline; 4 age-matched mice with mild proteinuria served as controls. Serum creatinine and urinary protein levels were analyzed, and kidney histological changes were observed by periodic acid–Schiff and Sirius Red staining. SA-β-Gal was detected via histochemistry. Glomerular expression of collagen IV, α-SMA, and nephrin was analyzed by immunohistochemistry, and glomerular complement C3 deposition was tested by immunofluorescence. The relationships between SA-β-Gal expression and renal function or glomerular lesion markers were determined by Spearman’s correlation analysis. RESULTS: Mice with severe proteinuria exhibited glomerular segmental sclerosis and endothelial cell proliferation. DEX administration suppressed these lesions but had no significant effect on 24-hour urinary protein levels. The elevated glomerular expression of SA-β-Gal in proteinuric mice was attenuated by DEX treatment. In addition, DEX treatment markedly downregulated glomerular C3 deposition and collagen IV and α-SMA expression, while significantly increasing nephrin expression. Furthermore, SA-β-Gal expression was positively correlated with urinary protein levels and expression of α-SMA. CONCLUSIONS: Accelerated senescence of glomerular cells may contribute to glomerular injury in LN. International Scientific Literature, Inc. 2018-09-28 /pmc/articles/PMC6180956/ /pubmed/30265659 http://dx.doi.org/10.12659/MSM.909353 Text en © Med Sci Monit, 2018 This work is licensed under Creative Common Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0 (https://creativecommons.org/licenses/by-nc-nd/4.0/) ) |
spellingShingle | Animal Study Yang, Chen Xue, Jing An, Ning Huang, Xi-jie Wu, Zhi-hong Ye, Lin Li, Zhi-hang Wang, Shu-jun Pan, Qing-jun Liang, Dong Liu, Hua-feng Accelerated Glomerular Cell Senescence in Experimental Lupus Nephritis |
title | Accelerated Glomerular Cell Senescence in Experimental Lupus Nephritis |
title_full | Accelerated Glomerular Cell Senescence in Experimental Lupus Nephritis |
title_fullStr | Accelerated Glomerular Cell Senescence in Experimental Lupus Nephritis |
title_full_unstemmed | Accelerated Glomerular Cell Senescence in Experimental Lupus Nephritis |
title_short | Accelerated Glomerular Cell Senescence in Experimental Lupus Nephritis |
title_sort | accelerated glomerular cell senescence in experimental lupus nephritis |
topic | Animal Study |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6180956/ https://www.ncbi.nlm.nih.gov/pubmed/30265659 http://dx.doi.org/10.12659/MSM.909353 |
work_keys_str_mv | AT yangchen acceleratedglomerularcellsenescenceinexperimentallupusnephritis AT xuejing acceleratedglomerularcellsenescenceinexperimentallupusnephritis AT anning acceleratedglomerularcellsenescenceinexperimentallupusnephritis AT huangxijie acceleratedglomerularcellsenescenceinexperimentallupusnephritis AT wuzhihong acceleratedglomerularcellsenescenceinexperimentallupusnephritis AT yelin acceleratedglomerularcellsenescenceinexperimentallupusnephritis AT lizhihang acceleratedglomerularcellsenescenceinexperimentallupusnephritis AT wangshujun acceleratedglomerularcellsenescenceinexperimentallupusnephritis AT panqingjun acceleratedglomerularcellsenescenceinexperimentallupusnephritis AT liangdong acceleratedglomerularcellsenescenceinexperimentallupusnephritis AT liuhuafeng acceleratedglomerularcellsenescenceinexperimentallupusnephritis |