Study of laminin-5 in keratinocyte migration

• Project/Area Number: 14570798
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Dermatology
• Research Institution: Chiba university
• Principal Investigator: UTANI Atsushi Chiba University, Graduate School of Medicine, Associate Professor, 大学院・医学研究院, 助教授 (10292707)
• Co-Investigator(Kenkyū-buntansha): NOMIZU Motoyoshi Hokkaido University, Graduate School of Environmental Earth Science, Associate Professor, 大学院・地球環境科学研究科, 助教授 (00311522)
• Project Period (FY): 2002 – 2003
• Project Status: Completed (Fiscal Year 2003)
• Budget Amount: ¥3,500,000 (Direct Cost: ¥3,500,000); Fiscal Year 2003: ¥1,500,000 (Direct Cost: ¥1,500,000); Fiscal Year 2002: ¥2,000,000 (Direct Cost: ¥2,000,000)
• Keywords: Matrix / laminin-5 / MMP / MAPK / ラミニン / シンデカン

Research Abstract

The LG4 module of the laminin a3 chain (a3 LG4), a component of epithelial-specific laminin-5, has cell attachment activity and binds syndecan. Here, we show that recombinant a3 LG4 and a 19-mer synthetic peptide (A3G756) within a3 LG4 active for syndecan binding increased the expression of matrix metalloproteinase-1 (MMP-1) in keratinocytes and fibroblasts. This induction was inhibited by heparin and required de novo synthesis of proteins. In keratinocytes, A3G756 upregulated IL-1b and MMP-1 expression and an IL-1 receptor antagonist thoroughly inhibited A3G756-mediated induction of MMP-1. A3G756 also activated p38 mitogen-activated protein kinase (p38MAPK) and extracellular signal-related kinase (Erk). Studies with specific inhibitors of MAPKs showed that p38MAPK activation was necessary for both IL-1b and MMP-1 induction, but Erk activation was required only for MMP-1 induction. In fibroblasts, IL-1 receptor antagonist did not block A3G756-mediated induction of MMP-1. These results indicated that induction of MMP-1 by a3 LG4 is mediated through the IL-1b autocrine loop in keratinocytes but the mechanism of the induction in fibroblasts is different. Our study suggests that the laminin a3 LG4 module may play an important role in tissue remodeling by inducing MMP-1 expression during wound healing.

Research Products

• [Publications] Kato K, Utani A, Suzuki N, et al.: "Identification of Neurite Outgrowth Promoting Sites on the Laminin alpha3 Chain G Domain."Biochemistry. 41. 10747-10753 (2002)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Utani A, Momota Y, et al.: "Laminin α3 LG4 module induces matrix metalloproteinase1 (MMP1) through MAPK signaling."J Biol Chem. 278. 34483-34490 (2003)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Suzuki N, Ichikawa N, et al.: "Syndecan binding sites on the laminin α1 chain G domain."Biochemistry. 42. 12625-12633 (2003)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Suzuki N, Nakatsuka H, et al.: "Biological activities of homologous loop regions in the laminin alpha chain"J Biol Chem. 278. 45697-45705 (2003)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Matsuura H, Momota Y, et al.: "Localization of the laminin α4 chain in the skin and identification of a heparin-dependent cell adhesion site"J Invest Dermatol. (In press). (2004)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Kato K, Utani A, Suzuki N, Mochizuki M, Yanada M, Nishi N, Matsuura H, Shinkai H, Nomizu M.: "Identification of Neurite Outgrowth Promoting Sites on the Laminin alpha3 Chain G Domain."Biochemistry. 41. 10747-10753 (2002)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Utani A, Momota Y, Endo H, Kasuya Y, Beck K, Suzuki N, Nomizu M, Shinkai H.: "Laminin a3 LG4 module induces matrix metalloproteinase 1 (MMP1) through MAPK signaling."J Biol Chem. 278. 34483-34490 (2003)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Suzuki N, Ichikawa N, Kasai S, Yamada M, Nishi N, Morioka H, Yamashita H, Kitagawa Y, Utani A, Hoffman MP, Nomizu M.: "Syndecan binding sites on the laminin a1 chain G domain."Biochemistry. 42. 12625-12633 (2003)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Suzuki N, Nakatsuka H, Mochizuki M, Nishi N, Kadoya Y, Utani A, Oishi S, Fujii N, Kleinman HK, Nomizu M: "Biological activities of homologous loop regions in the laminin alpha chain G domains."J Biol Chem. 278. 45697-45705 (2003)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Matsuura H, Momota Y, Murata K, Matsushima H, Suzuki N, Nomizu M, Shinkai H, Utani A.: "Localization of the laminin a4 chain in the skin and identification of a heparin-dependent cell adhesion site within the laminin a4 chain C-terminal LG4 module."J Invest Dermatol. (in press). (2004)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Kato K, Utani A, Suzuki N, et al.: "Identification of Neurite Outgrowth Promoting Sites on the Laminin al pha3 Chain G Domain."Biochemistry. 41. 10747-10753 (2002)
• [Publications] Utani A, Momota Y, et al.: "Laminin α3 LG4 module induces matrix metalloproteinase1 (MMP1) through MAPK signaling."J Biol Chem. 278. 34483-34490 (2003)
• [Publications] Suzuki N, Ichikawa N, et al.: "Syndecan binding sites on the laminin α1 chain G domain."Biochemistry. 42. 12625-12633 (2003)
• [Publications] Suzuki N, Nakatsuka H, et al.: "Biological activities of homologous loop regions in the laminin alpha chain."J Biol Chem. 278. 45697-45705 (2003)
• [Publications] Matsuura H, Momota Y, et al.: "Localization of the laminin α4 chain in the skin and identification of a heparin-dependent cell adhesion site."J Invest Dermatol. (In press). (2004)
• [Publications] KATO K, UTANI A et al.: "Identification of Neurite outgrowth promoting sites on the laminin α3 chain G domain"Biochemistry. 41・35. 12747-12753 (2002)
• [Publications] OKAZAKI I, SUZUKI N, et al.: "Identification of Biologically active sequences in the laminin α4 chain G domain"J. Biol. Chem.. 277. 37070-37078 (2002)