Human TIMP-3 is expressed during fetal development, hair growth cycle, and cancer progression.
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.
Airola
K
K
Department of Dermatology, Helsinki University Central Hospital, Helsinki, Finland.
Ahonen
M
M
Johansson
N
N
Heikkilä
P
P
Kere
J
J
Kähäri
V M
VM
Saarialho-Kere
U K
UK
D000328:Adult; D015152:Blotting, Northern; D001842:Bone and Bones / Q000196:embryology / Q000378:metabolism; D002280:Basal Cell Carcinoma / Q000378:metabolism; D002294:Carcinoma, Squamous Cell / Q000378:metabolism; D002356:Cartilage / Q000196:embryology / Q000378:metabolism; D002478:Cells, Cultured; D003238:Connective Tissue / Q000196:embryology / Q000378:metabolism; D005333:Fetus / Q000378:metabolism*; D018859:Hair Follicle / Q000196:embryology / Q000254:growth & development / Q000378:metabolism*; D006801:Humans; D017403:In Situ Hybridization; D007375:Interleukin-1 / Q000494:pharmacology; D015603:Keratinocytes / Q000187:drug effects / Q000378:metabolism; D007668:Kidney / Q000196:embryology / Q000378:metabolism; D008648:Mesoderm / Q000378:metabolism; D011480:Protease Inhibitors / Q000378:metabolism*; D012333:RNA, Messenger / Q000032:analysis; D012878:Skin Neoplasms / Q000378:metabolism* / Q000473:pathology; D013997:Time Factors; D014018:Tissue Distribution; D019717:Tissue Inhibitor of Metalloproteinase-3 / Q000378:metabolism*; D016212:Transforming Growth Factor beta / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D007375:Interleukin-1; D011480:Protease Inhibitors; D012333:RNA, Messenger; D019717:Tissue Inhibitor of Metalloproteinase-3; D016212:Transforming Growth Factor beta; D014409:Tumor Necrosis Factor-alpha