title: Induction of heat shock protein 47 synthesis by TGF-beta and IL-1 beta via enhancement of the heat shock element binding activity of heat shock transcription factor 1.
abstract: With most immunological reactions, tissue fibrosis, collagen overproduction caused by immune cytokines, is inevitably associated. Among the various immune cytokines, heat shock protein 47 (HSP47) is a procollagen-specific molecular chaperon and is essential for secretion of procollagen from cells. Induction of HSP47 by TGF-beta has been previously reported in rat skeletal myoblasts and mouse osteoblasts, but not in human diploid fibroblasts. As for IL-1beta, its effect on HSP47 has not been elucidated. In the present study, using human embryonic lung fibroblast cells, we first disclosed that both TGF-beta and IL-1beta induced HSP47 synthesis. We then revealed that the binding of the heat shock element (HSE) by heat shock transcription factor 1 (HSF1) was enhanced by both cytokines. We further demonstrated that trimer formation of HSF1, which is essential for its binding to HSE, was induced by these cytokines. The enhancement of HSP47 synthesis and their trimer formation of HSF1 were augmented by using a combination of both cytokines. Collectively, TGF- beta and IL-1beta were found to induce trimer formation of HSF1 which in turn bound to HSE of HSP47, resulting in the enhancement of HSP47 expression. Thus, HSP47 could well be a good candidate for molecular targeting in controlling tissue fibrosis, given that both principal fibrinogenetic cytokines (TGF-beta, IL-1beta) are commonly involved in its induction through HSF1 trimerization.
authors: Department of Internal Medicine (Section 4) and Clinical Diagnosis Medicine, Sapporo Medical University School of Medicine, South-1, West-16, Sapporo 060-8543, Japan.
authors: Hiroyoshi
authors: H
authors: Sasaki
authors: Tsutomu
authors: T
authors: Sato
authors: Naofumi
authors: N
authors: Yamauchi
authors: Tetsuro
authors: T
authors: Okamoto
authors: Daisuke
authors: D
authors: Kobayashi
authors: Satoshi
authors: S
authors: Iyama
authors: Junji
authors: J
authors: Kato
authors: Takuya
authors: T
authors: Matsunaga
authors: Rishu
authors: R
authors: Takimoto
authors: Tetsuji
authors: T
authors: Takayama
authors: Katsuhisa
authors: K
authors: Kogawa
authors: Naoki
authors: N
authors: Watanabe
authors: Yoshiro
authors: Y
authors: Niitsu
mesh_terms: D002460:Cell Line; D004268:DNA-Binding Proteins / Q000096:biosynthesis / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004338:Drug Combinations; D004622:Embryo, Mammalian; D005347:Fibroblasts; D005786:Gene Expression Regulation / Q000502:physiology; D050958:HSP47 Heat-Shock Proteins; D000076249:Heat Shock Transcription Factors; D006360:Heat-Shock Proteins / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology / Q000502:physiology*; D011485:Protein Binding / Q000502:physiology; D012333:RNA, Messenger / Q000096:biosynthesis; D012045:Regulatory Sequences, Nucleic Acid / Q000502:physiology*; D013997:Time Factors; D014157:Transcription Factors; D016212:Transforming Growth Factor beta / Q000494:pharmacology / Q000502:physiology*
chemical_list: D004268:DNA-Binding Proteins; D004338:Drug Combinations; C000619706:HSF1 protein, human; D050958:HSP47 Heat-Shock Proteins; D000076249:Heat Shock Transcription Factors; D006360:Heat-Shock Proteins; C000619709:Hsf1 protein, rat; D007375:Interleukin-1; D012333:RNA, Messenger; C494660:SERPINH1 protein, human; D014157:Transcription Factors; D016212:Transforming Growth Factor beta