Tubulointerstitial Macrophage Accumulation is Regulated by Sequentially Expressed Osteopontin and Macrophage Colony-Stimulating Factor: Implication for the Role of Atorvastatin
| Autor: | Ru-han Jia, Shaojiang Tian, Guohua Ding, Guili Chu |
|---|---|
| Rok vydání: | 2006 |
| Předmět: |
Macrophage colony-stimulating factor
medicine.medical_specialty Pathology Atorvastatin Immunology Inflammation Biology Rats Sprague-Dawley Research Communication Fibrosis Internal medicine lcsh:Pathology medicine Animals Pyrroles Osteopontin Cell Proliferation Reverse Transcriptase Polymerase Chain Reaction Macrophage Colony-Stimulating Factor Macrophages Cell Biology medicine.disease Immunohistochemistry Lipids Rats Kidney Tubules Endocrinology Gene Expression Regulation Heptanoic Acids Tubulointerstitial fibrosis biology.protein Hydroxymethylglutaryl-CoA Reductase Inhibitors medicine.symptom Infiltration (medical) lcsh:RB1-214 medicine.drug |
| Zdroj: | Mediators of Inflammation, Vol 2006 (2006) Mediators of Inflammation |
| ISSN: | 1466-1861 0962-9351 |
| Popis: | Infiltration and local proliferation are known factors that contribute to tubulointerstitial macrophage accumulation. This study explored the time course of these two contributors' roles as tubulointerstitial inflammation and fibrosis progressing, and evaluated the mechanisms of the protective effect of atorvastatin. Unilateral ureteral obstructive (UUO) rats were treated with atorvastatin (10 mg/Kg) or vehicle. Expression of osteopontin (OPN) and macrophage colony-stimulating factor (M-CSF) was evaluated by RT-PCR and immunohistochemistry. Immunohistochemistry staining of ED1 was used to assess macrophage accumulation in interstitium. Histological evaluation was performed to semiquantify tubulointerstitial fibrosis. The results showed that on day 3 after UUO operation, OPN expression significantly increased and positively correlated with the number of the interstitial ED1+cells, while on day 10, M-CSF expression upregulated and correlated with interstitial ED1+cells. In atorvastatin treatment group, the increments of these two factors were attenuated significantly at the two time points, respectively. ED1+cell accumulation and fibrosis also ameliorated in the treatment group. For all the samples of UUO and treatment group on day 10, ED1+cells also correlated with interstitial fibrosis scores. The results suggest that OPN may induce the early macrophage/monocyte infiltration and M-CSF may play an important role in regulating macrophage accumulation in later stage of UUO nephropathy. Statin treatment decreases interstitial inflammation and fibrosis, and this renoprotective effect may be mediated by downregulating the expression of OPN and M-CSF. |
| Databáze: | OpenAIRE |
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