Human TIMP-3 is expressed during fetal development, hair growth cycle, and cancer progression

J Histochem Cytochem. 1998 Apr;46(4):437-47. doi: 10.1177/002215549804600403.


We studied the expression and regulation of TIMP-3, a recently cloned member of the tissue inhibitor of the metalloproteinase family, during human fetal development and in various human tissues, with emphasis on epithelial structures. Expression of TIMP-3 mRNA was detected by in situ hybridization in developing bone, kidney, and various mesenchymal structures. At 16 weeks of gestation, ectoderm-derived cells of hair germs expressed TIMP-3 mRNA, and beginning from the twentieth week consistent expression was detected in epithelial outer root sheath cells of growing hair follicles. In normal adult human skin, expression of TIMP-3 mRNA was limited to hair follicles, starting at the early anagen (growing) phase and vanishing at the catagen (regressing) phase. TIMP-3 mRNA was not detected in benign hair follicle-derived tumors but was present in tumor cells of infiltrative basal cell carcinomas and in surrounding stromal cells in squamous cell carcinomas. Human primary keratinocytes in culture expressed TIMP-3 mRNAs, the levels of which were upregulated by transforming growth factor-beta (TGF-beta), whereas interleukin-1beta (IL-1beta) and tumor necrosis factor-alpha (TNF-alpha) had no effect. Our results suggest a role for TIMP-3 in connective tissue remodeling during fetal development, hair growth cycle, and cancer progression.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Blotting, Northern
  • Bone and Bones / embryology
  • Bone and Bones / metabolism
  • Carcinoma, Basal Cell / metabolism
  • Carcinoma, Squamous Cell / metabolism
  • Cartilage / embryology
  • Cartilage / metabolism
  • Cells, Cultured
  • Connective Tissue / embryology
  • Connective Tissue / metabolism
  • Fetus / metabolism*
  • Hair Follicle / embryology
  • Hair Follicle / growth & development
  • Hair Follicle / metabolism*
  • Humans
  • In Situ Hybridization
  • Interleukin-1 / pharmacology
  • Keratinocytes / drug effects
  • Keratinocytes / metabolism
  • Kidney / embryology
  • Kidney / metabolism
  • Mesoderm / metabolism
  • Protease Inhibitors / metabolism*
  • RNA, Messenger / analysis
  • Skin Neoplasms / metabolism*
  • Skin Neoplasms / pathology
  • Time Factors
  • Tissue Distribution
  • Tissue Inhibitor of Metalloproteinase-3 / metabolism*
  • Transforming Growth Factor beta / pharmacology
  • Tumor Necrosis Factor-alpha / pharmacology


  • Interleukin-1
  • Protease Inhibitors
  • RNA, Messenger
  • Tissue Inhibitor of Metalloproteinase-3
  • Transforming Growth Factor beta
  • Tumor Necrosis Factor-alpha