TY - JOUR
T1 - MiRNA-146a expression positively regulates tumor necrosis factor-α-induced interleukin-8 production in mesenchymal stem cells and differentiated lung epithelial-like cells
AU - Perng, Diahn Warng
AU - Yang, De Ming
AU - Hsiao, Yi Han
AU - Lo, Ting
AU - Lee, Oscar Kuang Sheng
AU - Wu, Mo Tzu
AU - Wu, Yu Chung
AU - Lee, Yu Chin
PY - 2012/11/1
Y1 - 2012/11/1
N2 - Bone marrow-derived mesenchymal stem cells (BM-MSC) can be differentiated into lung epithelial-like cells (MSC-EC) in vitro. The response of BM-MSC and MSC-EC to stimuli may vary because of their character and differentiation. We aimed to investigate the factors that may influence in vitro differentiation of BM-MSC to MSC-EC. We determined the response of BM-MSC, MSC-EC, bronchial epithelial cells, and alveolar epithelial cells to tumor necrosis factor (TNF)-α stimulation. We also investigated the changes in micro(mi)RNA-146a, miRNA-155, and TNF receptor 1 (TNFR1) expression after stimulation. Our results demonstrate that the addition of transforming growth factor-β1 and extracellular matrix collagen are required to facilitate such differentiation. After 3 weeks of culture, the morphological appearance and expression of airway epithelial markers, cytokeratin and Clara cell secretory protein, in MSC-EC were characteristics of lung epithelial cells. In response to TNF-α stimulation, the maximal interleukin (IL)-8 production by BM-MSC at the 24-h time point was 4.8 times greater compared with MSC-EC. TNF-α induced a significant increase in the expression of miRNA-146a in BM-MSC as compared with MSC-EC. miRNA-155 expression remained unchanged after stimulation. TNFR1 mRNA also significantly increased in BM-MSC after TNF-α stimulation. This was not observed in MSC-EC. Transfection with miRNA-146a mimics resulted in a significant increase of miRNA-146a expression and IL-8 production in both types of cells. In contrast, miRNA-146a inhibitors reduced miRNA-146a expression and IL-8 production. Overexpression of miRNA-146a, which positively regulates TNF-α-induced IL-8 release, may enhance the inflammatory response in both BM-MSC and MSC-EC. The expression of miRNA-146a and the response to stimuli may be modulated through mature differentiation of BM-MSC.
AB - Bone marrow-derived mesenchymal stem cells (BM-MSC) can be differentiated into lung epithelial-like cells (MSC-EC) in vitro. The response of BM-MSC and MSC-EC to stimuli may vary because of their character and differentiation. We aimed to investigate the factors that may influence in vitro differentiation of BM-MSC to MSC-EC. We determined the response of BM-MSC, MSC-EC, bronchial epithelial cells, and alveolar epithelial cells to tumor necrosis factor (TNF)-α stimulation. We also investigated the changes in micro(mi)RNA-146a, miRNA-155, and TNF receptor 1 (TNFR1) expression after stimulation. Our results demonstrate that the addition of transforming growth factor-β1 and extracellular matrix collagen are required to facilitate such differentiation. After 3 weeks of culture, the morphological appearance and expression of airway epithelial markers, cytokeratin and Clara cell secretory protein, in MSC-EC were characteristics of lung epithelial cells. In response to TNF-α stimulation, the maximal interleukin (IL)-8 production by BM-MSC at the 24-h time point was 4.8 times greater compared with MSC-EC. TNF-α induced a significant increase in the expression of miRNA-146a in BM-MSC as compared with MSC-EC. miRNA-155 expression remained unchanged after stimulation. TNFR1 mRNA also significantly increased in BM-MSC after TNF-α stimulation. This was not observed in MSC-EC. Transfection with miRNA-146a mimics resulted in a significant increase of miRNA-146a expression and IL-8 production in both types of cells. In contrast, miRNA-146a inhibitors reduced miRNA-146a expression and IL-8 production. Overexpression of miRNA-146a, which positively regulates TNF-α-induced IL-8 release, may enhance the inflammatory response in both BM-MSC and MSC-EC. The expression of miRNA-146a and the response to stimuli may be modulated through mature differentiation of BM-MSC.
UR - http://www.scopus.com/inward/record.url?scp=84868517795&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84868517795&partnerID=8YFLogxK
U2 - 10.1089/ten.tea.2011.0634
DO - 10.1089/ten.tea.2011.0634
M3 - Article
C2 - 22876745
AN - SCOPUS:84868517795
SN - 1937-3341
VL - 18
SP - 2259
EP - 2267
JO - Tissue Engineering - Part A
JF - Tissue Engineering - Part A
IS - 21-22
ER -