The proliferation and differentiation of placental-derived multipotent cells into smooth muscle cells on fibrillar collagen.
Type I collagen constitutes a major portion of the extracellular matrix (ECM) in arterial wall and it is the major substrate for cell growth and differentiation. The goal of this study was to evaluate the differentiation and proliferation of placenta-derived multipotent cells (PDMCs) on polymerized type I collagen fibrils and monomer collagen. PDMCs grown on both polymerized collagen and monomer collagen with transforming growth factor (TGF)-beta treatment increases the expression of smooth muscle cell (SMC)-specific markers, including calponin, alpha-smooth muscle actin (alpha-SMA) and smooth muscle-myosin heavy chain (SM-MHC). Polymerized collagen increased the expressions of p21(CIP1) and p27(KIP1); decreased cyclin A, cyclin D1, cyclin-dependent protein kinase 2 (Cdk2); and led to G(0)/G(1) arrest in PDMCs. Furthermore, PDMC-differentiated SMCs exhibited significant collagen contractility in the presence or absence of endothelin-1 (ET-1) stimulation. By using specific inhibitors and small interfering RNA (siRNA), we demonstrated that p38 MAPK pathway and serum response factor (SRF)-DNA binding activity is critical for the polymerized collagen-induced PDMC differentiation into SMCs. Thus, polymerized collagen exhibits the great potential in inducing PDMCs differentiation into SMCs, and exerts anti-proliferative effect on PDMC-differentiated SMCs.
Chou
Mou-Tsy
MT
Department of Gynecology, St. Martin De Porres Hospital, Chiayi City, Taiwan.
Chang
Sheng-Nan
SN
Ke
Chieh
C
Chang
Hsin-I
HI
Sung
Mao-Lin
ML
Kuo
Hsing-Chun
HC
Chen
Cheng-Nan
CN
D000818:Animals; D000077214:Becaplermin; D002135:Calcium-Binding Proteins / Q000378:metabolism; D018929:Cell Culture Techniques; D018797:Cell Cycle Proteins / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology*; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D024042:Collagen Type I / Q000378:metabolism; D005260:Female; D024022:Fibrillar Collagens / Q000378:metabolism*; D006801:Humans; D008840:Microfilament Proteins / Q000378:metabolism; D039902:Multipotent Stem Cells / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D009119:Muscle Contraction / Q000187:drug effects / Q000502:physiology; D032389:Myocytes, Smooth Muscle / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D010920:Placenta / Q000166:cytology*; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology; D011247:Pregnancy; D020574:Proto-Oncogene Proteins c-sis; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D026362:Serum Response Factor / Q000235:genetics / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000494:pharmacology; D048051:p38 Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism; D000096985:Calponins
D000077214:Becaplermin; D002135:Calcium-Binding Proteins; D018797:Cell Cycle Proteins; D024042:Collagen Type I; D024022:Fibrillar Collagens; D008840:Microfilament Proteins; D010982:Platelet-Derived Growth Factor; D020574:Proto-Oncogene Proteins c-sis; D034741:RNA, Small Interfering; D026362:Serum Response Factor; D016212:Transforming Growth Factor beta; D048051:p38 Mitogen-Activated Protein Kinases; D000096985:Calponins