High glucose downregulates myocardin expression in rat glomerular mesangial cells via the ERK signaling pathway
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Ming Li1,2,*, Lijuan Xu2,*, Guowei Feng3,4, Yan Zhang2, Xin Wang2 and Yuebing Wang2
1School of Basic Medical Sciences, Hebei University, Baoding, China
2Department of Biochemistry, School of Medicine, Nankai University, Tianjin, China
3Department of Genitourinary Oncology, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, China
4Tianjin’s Clinical Research Center for Cancer, Tianjin, China
*These authors have contributed equally to this work
Yuebing Wang, email: [email protected]
Keywords: extracellular signal-regulated kinase (ERK), glomerular mesangial cells, high glucose, myocardin, smooth muscle α-actin (SM α-actin)
Received: June 21, 2017 Accepted: July 26, 2017 Published: August 24, 2017
Mesangial cells (MCs), which are vascular smooth muscle-derived cells, occupy the central position in the glomerulus. Diabetic nephropathy (DN) is one of the most common diabetes complications and is likely attributed to the loss of MC contractility. Myocardin stimulates downstream vascular smooth muscle genes and regulates the contractility of vascular smooth muscle cells. Therefore, we hypothesized that myocardin is expressed in MCs and that high glucose is involved in the regulation of myocardin and downstream contractile genes in the context of DN. Confocal microscopy revealed that myocardin is expressed in rat MCs. Western blot and RT-qPCR analyses showed that treatment with 30 mM D-glucose significantly downregulated the mRNA and protein levels of myocardin and downstream SM α-actin. As an isotonic contrast, 30 mM mannitol did not affect myocardin mRNA levels but did downregulate myocardin protein levels. Treatment with 30 mM mannitol also downregulated SM α-actin mRNA and protein levels. Conversely, as another isotonic contrast, 30 mM L-glucose also had no effect on myocardin and SM α-actin expression in MCs. The extracellular signal-regulated kinase (ERK) pathway was activated by treatment with 30 mM D-glucose or mannitol, while specific inhibitors of the ERK pathway (PD98059) compromised the downregulation of myocardin and SM α-actin triggered by high glucose or mannitol. Thus we revealed that myocardin is expressed in MCs and that high glucose downregulates myocardin expression and downstream contractile protein SM α-actin via the ERK pathway. Our results suggest a novel mechanism for high glucose inhibition of MC contraction, which contributes to DN pathogenesis.
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