Regulation of hepatocyte cell cycle progression and differentiation by type I collagen structure.

摘要: Cell behavior is strongly influenced by the extracellular matrix (ECM) to which cells adhere. Both chemical determinants within ECM molecules and mechanical properties of network regulate cellular response, including proliferation, differentiation, apoptosis. Type I collagen most abundant protein in body with a complex structure that can be altered vivo proteolysis, cross-linking, other processes. Because collagen's dynamic nature, it important define changes cell response different structures its underlying mechanisms. This chapter reviews current knowledge potential mechanisms type affects behavior, presents data elucidate specific intracellular signaling pathways differentially hepatocyte cycle progression differentiation. A polymerized fibrillar (collagen gel) induces highly differentiated but growth-arrested phenotype primary hepatocytes, whereas film monomeric adsorbed rigid dish promotes dedifferentiation. Studies presented here demonstrate kinase (PKA) activity significantly elevated hepatocytes on gel relative film, inhibition this PKA promote gel. Additional studies are examine differentiation increased rigidity fiber cross-linking. Potential these responses their implications discussed.