Overexpression of miR-126 promotes the differentiation of mesenchymal stem cells toward endothelial cells via activation of PI3K/Akt and MAPK/ERK pathways and release of paracrine factors
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Feng Huang
und
Jian-ping Huang
Abstract
The endothelial cell (EC)-specific miRNA, miR-126, is known to promote angiogenesis in response to angiogenic factors by repressing negative regulators of signal transduction pathways; however, whether miR-126 might regulate the differentiation of stem cells toward endothelial lineage remains unknown. To answer this question, in this study mesenchymal stem cells (MSCs) harvested from C57BL/6 mouse bone marrow were transfected with miR-126 (MSCmiR-126) using recombinant lentiviral vectors. Results showed the para-secretion and the expression levels of phosphorylated PI3K p85, Akt, p38, ERK1 protein in the MSCmiR-126 group were dramatically increased when compared with the control group. With half culture medium refreshed every 3 days, a small number of 6-day-cultured MSCmiR-126 differentiated into endothelial-like cells and most of 9-day-cultured MSCmiR-126 formed a cobblestone-like structure. These differentiated cells evidently expressed EC-specific makers and possessed mature ECs function, while inhibition of paracrine factors suppressed the MSC-EC differentiation. Strikingly, the increased secretion of MSCmiR-126 and their endothelial-differentiated potential were deprived by using a PI3K or MEK chemical inhibitor. Our results suggest that overexpression of miR-126 agumenting the endothelial differentiation of MSCs might in part be attributable to the activation of PI3K/Akt and MAPK/ERK pathways and an increased release of paracrine factors.
This work was supported by 2009 National Nature Scientific Funding of China (No. 30871053).
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Artikel in diesem Heft
- Masthead
- Masthead
- Reviews
- Imaging the invisible: resolving cellular microcompartments by superresolution microscopy techniques
- Structure and function of MK5/PRAK: the loner among the mitogen-activated protein kinase-activated protein kinases
- Functional ribosome biogenesis is a prerequisite for p53 destabilization: impact of chemotherapy on nucleolar functions and RNA metabolism
- Interleukin-6 and interleukin-11: same same but different
- Cathepsin K: a unique collagenolytic cysteine peptidase
- Research Articles/Short Communications
- Protein Structure and Function
- The active form of goat insulin-like peptide 3 (INSL3) is a single-chain structure comprising three domains B-C-A, constitutively expressed and secreted by testicular Leydig cells
- Molecular Medicine
- Zinc-dependent contact system activation induces vascular leakage and hypotension in rodents
- Cell Biology and Signaling
- ACE inhibition enhances bradykinin relaxations through nitric oxide and B1 receptor activation in bovine coronary arteries
- Changes in COX-2 and oxidative damage factors during differentiation of human mesenchymal stem cells to hepatocyte-like cells is associated with downregulation of P53 gene
- Overexpression of miR-126 promotes the differentiation of mesenchymal stem cells toward endothelial cells via activation of PI3K/Akt and MAPK/ERK pathways and release of paracrine factors
- Novel Techniques
- Synthesis of a novel benzodifuran derivative and its molecular recognition of poly rA RNA
