Journal
JOURNAL OF CELLULAR AND MOLECULAR MEDICINE
Volume 22, Issue 10, Pages 4840-4855Publisher
WILEY
DOI: 10.1111/jcmm.13747
Keywords
apoptosis; diabetic nephropathy; kidney injury; miR-124a; Notch; podocyte
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Funding
- National Natural Science Foundation of China [81200528]
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BMSCs are important in replacement therapy of diabetic nephropathy (DN). MiR-124a exerts effect on the differentiation capability of pancreatic progenitor cells. The objective of this study was to explore the molecular mechanisms, the functions of miR-124a and bone marrow mesenchymal stem cells (BMSCs) in the treatment of DN. Characterizations of BMSCs were identified using the inverted microscope and flow cytometer. The differentiations of BMSCs were analysed by immunofluorescence assay and DTZ staining. The expression levels of islet cell-specific transcription factors, apoptosis-related genes, podocytes-related genes and Notch signalling components were detected using quantitative real-time reverse transcription PCR (qRT-PCR) and Western blot assays. The production of insulin secretion was detected by adopting radioimmunoassay. Cell proliferation and apoptosis abilities were detected by CCK-8, flow cytometry and TUNEL assays. We found that BMSCs was induced into islet-like cells and that miR-124a could promote the BMSCs to differentiate into islet-like cells. BMSCs in combination with miR-124a regulated islet cell-specific transcription factors, apoptosis-related genes, podocytes-related genes as well as the activity of Notch signalling pathway. However, BMSCs in combination with miR-124a relieved renal lesion caused by DN and decreased podocyte apoptosis caused by HG. The protective effect of BMSCs in combination with miR-124a was closely related to the inactivation of Notch signalling pathway. MSCs in combination with miR-124a protected kidney tissue from impairment and inhibited nephrocyte apoptosis in DN.
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