Journal
FRONTIERS IN BIOSCIENCE-LANDMARK
Volume 19, Issue -, Pages 727-733Publisher
FRONTIERS IN BIOSCIENCE INC
DOI: 10.2741/4239
Keywords
Three-dimensional collagen gel; Denatured Collagen; Fibroblast Cells
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Funding
- China National Nature Scientific Grants [81071567, 81071566, 30872685, 30872686, 81000838, 81101433]
- Key Project of Chinese National Programs for Fundamental Research and Development( 973 program) [2012CB518105]
- National Science & Technology Pillar Program [2012BAI11B00]
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Extracellular matrix is one of the key environmental factors influencing cell survival and provides signals for cell morphological change, migration, proliferation and differentiation. However, the mechanism through which denatured collagen modulates the biological properties of fibroblasts, is unclear. We investigated the regulation of human fibroblast differentiation in vitro grown in collagen gels with different properties. The break modulus of collagen with denatured collagen and half-load normal collagen was reduced compared with that of normal collagen gel. Fibroblasts cultured in denatured collagen gels showed increased expression of matrix metalloproteinase9(MMP-9), tissue inhibitor of metalloproteinase 2(TIMP2), alpha-smooth muscle actin(alpha-SMA), osteoblast cadherin, phosphorylated Myosin phosphatase target subunit1(p-MYPT1), connective tissue growth factor, type I collagen, type III collagen, a-smooth muscle actin messenger RNA, RhoA, rho-associated protein kinase, and transforming growth factor beta receptors 1 and 2 compared with that in cells cultured in normal collagen gel. But there was no significant difference regarding expression level between denatured collagen gel and half-load normal collagen gel. These findings suggest that the change in break modulus caused by decreasing normal collagen concentration may be the key factor inducing fibroblast differentiation.
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