title: The change of break modulus drives human fibroblast differentiation in 3D collagen gels.
abstract: 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), α-smooth muscle actin (α-SMA), osteoblast cadherin, phosphorylated Myosin phosphatase target subunit1 (p-MYPT1), connective tissue growth factor, type I collagen, type III collagen, α-smooth muscle actin messenger RNA, RhoA, rho-associated protein kinase, and transforming growth factor β 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.
authors.affiliation: Department of Burn and Plastic Surgery, Ruijin Hospital, Shanghai Burn Institute, Shanghai Jiaotong University School of Medicine, Shanghai, China.
authors.forename: Zhi-yong
authors.initials: ZY
authors.lastname: Wang
authors.affiliation: Rehabilitation Center of Plastic and Burn, First Affiliated Hospital of GuangXi Medical University, Nanning, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Wei
authors.affiliation: Department of Burn and Plastic Surgery, Ruijin Hospital, Shanghai Burn Institute, Shanghai Jiaotong University School of Medicine, Shanghai, China.
authors.forename: Bo
authors.initials: B
authors.lastname: Yuan
authors.affiliation: Department of Burn and Plastic Surgery, Ruijin Hospital, Shanghai Burn Institute, Shanghai Jiaotong University School of Medicine, Shanghai, China.
authors.forename: Xi-Qiao
authors.initials: XQ
authors.lastname: Wang
authors.affiliation: Department of Burn and Plastic Surgery, Ruijin Hospital, Shanghai Burn Institute, Shanghai Jiaotong University School of Medicine, Shanghai, China.
authors.forename: Yin-kai
authors.initials: YK
authors.lastname: Liu
authors.affiliation: Department of Burn and Plastic Surgery, Ruijin Hospital, Shanghai Burn Institute, Shanghai Jiaotong University School of Medicine, Shanghai, China.
authors.forename: Jiao-Yun
authors.initials: JY
authors.lastname: Dong
authors.affiliation: Department of Burn and Plastic Surgery, Ruijin Hospital, Shanghai Burn Institute, Shanghai Jiaotong University School of Medicine, Shanghai, China.
authors.forename: Fei
authors.initials: F
authors.lastname: Song
authors.affiliation: Department of Burn and Plastic Surgery, Ruijin Hospital, Shanghai Burn Institute, Shanghai Jiaotong University School of Medicine, Shanghai, China.
authors.forename: Yu-zhi
authors.initials: YZ
authors.lastname: Jiang
authors.affiliation: Department of Burn and Plastic Surgery, Ruijin Hospital, Shanghai Burn Institute, Shanghai Jiaotong University School of Medicine, Shanghai, China.
authors.forename: Shu-liang
authors.initials: SL
authors.lastname: Lu
mesh_terms: D001483:Base Sequence; D002454:Cell Differentiation; D002478:Cells, Cultured; D003094:Collagen / Q000378:metabolism*; D017931:DNA Primers; D005347:Fibroblasts / Q000166:cytology*; D006801:Humans; D060888:Real-Time Polymerase Chain Reaction
chemical_list: D017931:DNA Primers; D003094:Collagen