miR-124a enhances therapeutic effects of bone marrow stromal cells transplant on diabetic nephropathy-related epithelial-to-mesenchymal transition and fibrosis.
J Cell Biochem
; 121(1): 299-312, 2020 01.
Article
em En
| MEDLINE
| ID: mdl-31190436
ABSTRACT
BACKGROUND:
Epithelial-to-mesenchymal transition (EMT) has been gradually considered as one of the major pathways that causes the production of interstitial myofibroblasts in diseased kidneys. MATERIALS ANDMETHODS:
The study was done to investigate the effect of a bone marrow stromal cell (BMSCs) transplant on rat podocytes and diabetic nephropathy (DN) rats in high-glucose concentration, and to explore the effect of miR-124a on BMSC therapy. High glucose-injured podocytes and streptozotocin-induced DN rats have been respectively used as injury models in in vitro and in vivo studies. Podocyte viability was measured using the Cell Counting Kit-8 assay. Renal pathological examination was observed by HE staining and Masson staining. The messenger RNA and protein levels were determined via real-time polymerase chain reaction and Western blotting, respectively.RESULTS:
By mediating the activation of caveolin-1 (cav-1) and ß-catenin and affecting the expression levels of EMT biomarkers including p-cadherin, synaptopodin, fibroblast-specific protein-1, α-smooth muscle actin and snail, our in vitro study confirmed that miR-124a played a significant role in the treatment of high glucose-induced podocyte injury by BMSCs. The therapeutic effects of the BMSC transplant on DN rats were also proved to be further enhanced by miR-124a overexpression in BMSCs, and such a phenomenon was accompanied by the improvement of renal fibrosis and mitigation of DN-related kidney impairment. Regulation of fibronectin, collagen1, and EMT-related proteins was closely implicated with the mechanism, and the activation of cav-1 and ß-catenin was also possibly involved.CONCLUSION:
The study demonstrated the pivotal effect of miR-124a on BMSC therapy for DN rats via mitigating EMT and fibrosis. Our results provide a novel insight into how therapeutic effects of BMSCs can be improved at the posttranscriptional level.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Transplante de Medula Óssea
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MicroRNAs
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Nefropatias Diabéticas
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Transição Epitelial-Mesenquimal
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Glucose
Limite:
Animals
Idioma:
En
Revista:
J Cell Biochem
Ano de publicação:
2020
Tipo de documento:
Article
País de afiliação:
China