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High glucose levels stimulate extracellular matrix deposition in diabetic nephropathy.

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eMediNexus    11 December 2017

A new study published in the Molecular Medicine Reports investigated the association among factors – platelet-activating factor (PAF), protein kinase C (PKC)βI, transforming growth factor (TGF)‑β1, and aberrant extracellular matrix (ECM) deposition, in a diabetic nephropathy (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+PKCβI inhibitor LY333531; HG + LPC; PAF + HG + LPC; and PAF + HG + LPC + LY333531. The findings revealed that PKCβI and TGF‑β1 expressions were increased in the PAF + HG + LPC group compared to the other groups; whereas, this effect was neutralized in the presence of LY333531. While supernatant fibronectin and collagen IV levels were increased in the PAF + HG + LPC group than in the other group, which again was reversed by treatment with LY333531. Furthermore, in cells treated with PAF, HG, and LPC, PKCβI was translocated from the cytosol to the nucleus; however this effect was blocked when PKCβI expression was inhibited. Therefore, the results demonstrated that PAF stimulated ECM deposition in HMCs via activation of the PKC‑TGF‑β1 axis in a DN model.

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