Gremlin Regulates Podocyte Apoptosis via Transforming Growth Factor-β (TGF-β) Pathway in Diabetic Nephropathy
| Autor: | Hong Zhu, Xiao-Bing Wang, Jian-Hua Su, Wei Song |
|---|---|
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Pyridines 030232 urology & nephrology Apoptosis Podocyte Nephrin Transforming Growth Factor beta1 03 medical and health sciences Mice 0302 clinical medicine Transforming Growth Factor beta Lab/In Vitro Research medicine Animals Diabetic Nephropathies Benzodioxoles biology Chemistry Podocytes Lentivirus Microfilament Proteins Imidazoles Membrane Proteins General Medicine Transfection Cell biology Up-Regulation 030104 developmental biology medicine.anatomical_structure biology.protein Phosphorylation Cytokines Intercellular Signaling Peptides and Proteins Synaptopodin Signal transduction Gremlin (protein) Transforming growth factor Signal Transduction |
| Zdroj: | Medical Science Monitor : International Medical Journal of Experimental and Clinical Research |
| ISSN: | 1643-3750 |
| Popis: | BACKGROUND Gremlin has been reported to be up-regulated in glomerular mesangial cells in diabetic nephropathy (DN). However, the regulation of gremlin in podocytes is still rarely reported. This study aimed to investigate the underlying mechanisms by which gremlin mediates the pathogenesis of DN via transforming growth factor-β (TGF-β) signaling pathways. MATERIAL AND METHODS Lentiviral and RNAi transfection were performed to increase and decrease gremlin expression in high-glucose conditions. Expression at the mRNA and protein level was detected by RT-qPCR and Western blotting. RESULTS The expression of gremlin was significantly higher in high-glucose (HG, 30mM) than normal-glucose (NG, 5.5 mM) conditions. The gremlin overexpression significantly suppressed the expression of nephrin and synaptopodin. The phosphorylation of canonical TGF-b signaling pathway components, including Smad2/3 and MKK, was increased in the gremlin-overexpressing group. In addition, the expression levels of Bax and cleaved caspase-3 were also higher in the gremlin-overexpressing group. TGF-β pathway inhibitor (SB505124) significantly inhibited TGF-β pathway activity and enhanced the expression of nephrin and synaptopodin. CONCLUSIONS These results indicate that gremlin can aggravate podocyte lesions through the TGF-β signaling pathway, providing a novel therapeutic target for DN. |
| Databáze: | OpenAIRE |
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