Tranilast prevents renal interstitial fibrosis by blocking mast cell infiltration in a rat model of diabetic kidney disease.
Mol Med Rep
; 17(5): 7356-7364, 2018 05.
Article
en En
| MEDLINE
| ID: mdl-29568954
ABSTRACT
Renal interstitial fibrosis is a final pathway that is observed in various types of kidney diseases, including diabetic kidney disease (DKD). The present study investigated the effect of tranilast on renal interstitial fibrosis and the association between its role and mast cell infiltration in a rat model of DKD. A total of 30 healthy 6weekold male SpragueDawley rats were randomly divided into the following four groups Normal control group; DKD model group; lowdose tranilast group (200 mg/kg/day); and highdose tranilast group (400 mg/kg/day). The morphological alterations of tubulointerstitial fibrosis were evaluated by Masson's trichrome staining, while mast cell infiltration into the renal tubular interstitium was measured by toluidine blue staining and complement C3a receptor 1 (C3aR) immunohistochemical staining (IHC). The expression of fibronectin (FN), collagen I (ColI), stem cell factor (SCF) and protooncogene ckit (ckit) was detected by IHC, western blotting and reverse transcriptionquantitativepolymerase chain reaction. The results demonstrated that tubulointerstitial fibrosis and mast cell infiltration were observed in DKD model rats, and this was improved dosedependently in the tranilast treatment groups. The expression of FN, ColI, SCF and ckit mRNA and protein was upregulated in the tubulointerstitium of DKD model rats compared with the normal control rats, and tranilast inhibited the upregulated expression of these markers. Furthermore, the degree of SCF and ckit expression demonstrated a significant positive correlation with C3aRpositive mast cells and the markers of renal interstitial fibrosis. The results of the present study indicate that mast cell infiltration may promote renal interstitial fibrosis via the SCF/ckit signaling pathway. Tranilast may prevent renal interstitial fibrosis through inhibition of mast cell infiltration mediated through the SCF/c-kit signaling pathway.
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Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Antiinflamatorios no Esteroideos
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Nefropatías Diabéticas
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Ortoaminobenzoatos
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Riñón
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Mastocitos
Tipo de estudio:
Prognostic_studies
Límite:
Animals
Idioma:
En
Revista:
Mol Med Rep
Año:
2018
Tipo del documento:
Article