title: [Therapeutic strategy for fibrotic diseases by regulating the expression of collagen-specific molecular chaperone HSP47].
abstract: Through disruption of the hsp47 gene in mice, we found that HSP47, a collagen-specific molecular chaperone residing in the endoplasmic reticulum, is essential for mouse development. Improper triple helix formation was observed in hsp47-null embryos, and no collagen fibrils in the mesenchyme or basement membranes between the mesenchyme and epithelial cell layers were seen in those mice, which resulted in embryonic lethality. Interestingly, constitutive expression of HSP47 is always correlated with that of collagens in various cells or tissues. HSP47 is markedly up-regulated during the progression of fibrosis in the liver, kidney, lung, and so on. A preliminary experiment showed that down-regulation of HSP47 caused the reduction in the progression of fibrosis by down-regulating the accumulation of collagens in the tissues, which suggests a novel strategy for the therapy of fibrotic diseases including liver cirrhosis.
authors.affiliation: Department of Molecular and Cellular Biology, Institute for Frontier Medical Sciences, Kyoto University, Sakyo-ku, Kyoto 606-8397, Japan. nagata@frontier.kyoto-u.ac.jp
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Nagata
mesh_terms: D000818:Animals; D003094:Collagen / Q000737:chemistry / Q000378:metabolism; D018450:Disease Progression; D015536:Down-Regulation; D004721:Endoplasmic Reticulum / Q000378:metabolism; D050958:HSP47 Heat-Shock Proteins; D006360:Heat-Shock Proteins / Q000172:deficiency / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D008103:Liver Cirrhosis / Q000235:genetics* / Q000378:metabolism / Q000628:therapy; D051379:Mice; D017510:Protein Folding; D011658:Pulmonary Fibrosis / Q000235:genetics / Q000378:metabolism / Q000628:therapy; D015854:Up-Regulation
chemical_list: D050958:HSP47 Heat-Shock Proteins; D006360:Heat-Shock Proteins; C494660:SERPINH1 protein, human; C494661:Serpinh1 protein, mouse; D003094:Collagen