
| 10.3390/ijms21239225
http://scihub22266oqcxt.onion/10.3390/ijms21239225
 33287327!7731298!33287327
free
free
free
|  
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Int+J+Mol+Sci 2020 ; 21 (23): � Nephropedia Template TP
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Description of a Novel Mechanism Possibly Explaining the Antiproliferative Properties of Glucocorticoids in Duchenne Muscular Dystrophy Fibroblasts Based on Glucocorticoid Receptor GR and NFAT5 #MMPMID33287327Herbelet S; De Paepe B; De Bleecker JLInt J Mol Sci 2020[Dec]; 21 (23): � PMID33287327show ga
Glucocorticoids are drugs of choice in Duchenne muscular dystrophy (DMD), prolonging patients' ambulation. Their mode of action at the protein level is not completely understood. In DMD, muscle tissue is replaced by fibrotic tissue produced by fibroblasts, reducing mobility. Nuclear factor of activated T-cells 5 (NFAT5) is involved in fibroblast proliferation. By treating one DMD fibroblast cell culture and one of unaffected skeletal muscle fibroblasts with methylprednisolone (MP) or hydrocortisone (HC) for 24 h or 12 d, the antiproliferative properties of glucocorticoids could be unraveled. NFAT5 localization and expression was explored by immunocytochemistry (ICC), Western blotting (WB) and RT-qPCR. NFAT5 and glucocorticoid receptor (GR) colocalization was measured by ImageJ. GR siRNA was used, evaluating GR's influence on NFAT5 expression during MP and HC treatment. Cell proliferation was monitored by IncuCyte ZOOM. In DMD fibroblasts, treatment with MP for 24 h induced dots (ICC) positive for NFAT5 and colocalizing with GR. After 12 d of MP or HC in DMD fibroblasts, NFAT5 expression was decreased (RT-qPCR and WB) and growth arrest was observed (Incucyte ZOOM), whereas NFAT5 expression and cell growth remained unchanged in unaffected skeletal muscle fibroblasts. This study may help understand the antiproliferative properties of glucocorticoids in DMD fibroblasts.|Cell Proliferation/drug effects[MESH]|Cells, Cultured[MESH]|Dose-Response Relationship, Drug[MESH]|Fibroblasts/*drug effects/*metabolism[MESH]|Fluorescent Antibody Technique[MESH]|Glucocorticoids/*pharmacology[MESH]|Humans[MESH]|Hydrocortisone/pharmacology[MESH]|Methylprednisolone/pharmacology[MESH]|Muscle, Skeletal/drug effects/metabolism[MESH]|Muscular Dystrophy, Duchenne/genetics/metabolism[MESH]|Protein Binding[MESH]|Receptors, Glucocorticoid/*metabolism[MESH]
  
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