High glucose/lysophosphatidylcholine levels stimulate extracellular matrix deposition in diabetic nephropathy via plateletactivating factor receptor.
Mol Med Rep
; 17(2): 2366-2372, 2018 Feb.
Article
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| MEDLINE
| ID: mdl-29207067
ABSTRACT
Platelet-activating factor (PAF), protein kinase C (PKC)ßI, transforming growth factor (TGF)ß1 and aberrant extracellular matrix (ECM) deposition have been associated with diabetic nephropathy (DN). However, the mechanistic basis underlying this association remains to be elucidated. The present study investigated the association among the aforementioned factors in a DN model consisting of human mesangial cells (HMCs) exposed to high glucose (HG) and lysophosphatidylcholine (LPC) treatments. HMCs were divided into the following treatment groups Control; PAF; PAF+PKCßI inhibitor LY333531; HG + LPC; PAF + HG + LPC; and PAF + HG + LPC + LY333531. Cells were cultured for 24 h, and PKCßI and TGFß1 expression was determined using the reverse transcriptionquantitative polymerase chain reaction and western blotting. The expression levels of the ECMassociated molecules collagen IV and fibronectin in the supernatant were detected using ELISA analysis. Subcellular localization of PKCßI was assessed using immunocytochemistry. PKCßI and TGFß1 expression was increased in the PAF + HG + LPC group compared with the other groups (P<0.05); however, this effect was abolished in the presence of LY333531 (P<0.05). Supernatant fibronectin and collagen IV levels were increased in the PAF + HG + LPC group compared with the others (P<0.05); this was reversed by treatment with LY333531 (P<0.05). In cells treated with PAF, HG and LPC, PKCßI was translocated from the cytosol to the nucleus, an effect which was blocked when PKCßI expression was inhibited (P<0.05). The findings of the present study demonstrated that PAF stimulated ECM deposition in HMCs via activation of the PKCTGFß1 axis in a DN model.
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Base de datos:
MEDLINE
Asunto principal:
Glucemia
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Lisofosfatidilcolinas
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Glicoproteínas de Membrana Plaquetaria
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Receptores Acoplados a Proteínas G
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Nefropatías Diabéticas
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Matriz Extracelular
Tipo de estudio:
Observational_studies
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Prognostic_studies
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Risk_factors_studies
Idioma:
En
Revista:
Mol Med Rep
Año:
2018
Tipo del documento:
Article