title: Matriptase expression and zymogen activation in human pilosebaceous unit.
abstract: Studies of human genetic disorders and mouse models reveal the important roles of matriptase in hair growth. Here, we investigate matriptase expression and zymogen activation in hair follicles. We show: 1) layer-dependent distribution patterns, with much higher matriptase expression in cells of the outer root sheath and matrix cells of the hair bulb than in cells of the inner root sheath; 2) cycle-dependent expression patterns, with matriptase expressed in the anagen and catagen phases of the hair lifecycle, but not in the telogen phase; 3) reduced expression of the matriptase inhibitor, HAI-1, in the catagen phase, suggesting increased proteolytic activity in this phase; and 4) definitive matriptase zymogen activation patterns, with the highest matriptase activation observed in matrix cells and outer root sheath cells in the isthmus/bulge region. In sebaceous glands, matriptase is highly expressed in basal and ductal cells, with much lower expression in the differentiated, lipid-filled cells of the interior. We also show that matriptase potently activates hepatocyte growth factor (HGF) in vitro, and that the HGF receptor, c-Met, is co-expressed in those cells that express activated matriptase. Our observations suggest that the matriptase-HGF-c-MET pathway has the potential to be engaged, primarily in proliferative cells rather than terminally differentiated epithelial cells of the human pilosebaceous unit.
authors.affiliation: Department of Dermatology, (BYW), National Defense Medical Center, Taipei, Taiwan, ROC.
authors.forename: Bai-Yao
authors.initials: BY
authors.lastname: Wu
authors.forename: Shiao-Pieng
authors.initials: SP
authors.lastname: Lee
authors.forename: Hui-Chung
authors.initials: HC
authors.lastname: Hsiao
authors.forename: Han
authors.initials: H
authors.lastname: Chiu
authors.forename: Chi-Yung
authors.initials: CY
authors.lastname: Chen
authors.forename: Yee Hui
authors.initials: YH
authors.lastname: Yeo
authors.forename: Herng-Sheng
authors.initials: HS
authors.lastname: Lee
authors.forename: Ya-Wen
authors.initials: YW
authors.lastname: Chen
authors.forename: Malvika
authors.initials: M
authors.lastname: Kaul
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Kataoka
authors.forename: Michael D
authors.initials: MD
authors.lastname: Johnson
authors.forename: Jehng-Kang
authors.initials: JK
authors.lastname: Wang
authors.forename: Chen-Yong
authors.initials: CY
authors.lastname: Lin
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D002460:Cell Line; D049109:Cell Proliferation; D004789:Enzyme Activation; D004792:Enzyme Precursors / Q000378:metabolism*; D015971:Gene Expression Regulation, Enzymologic; D018859:Hair Follicle / Q000166:cytology / Q000201:enzymology / Q000254:growth & development; D006801:Humans; D015603:Keratinocytes / Q000166:cytology / Q000378:metabolism; D053491:Proteinase Inhibitory Proteins, Secretory / Q000378:metabolism; D019859:Proto-Oncogene Proteins c-met / Q000378:metabolism; D012627:Sebaceous Glands / Q000166:cytology / Q000201:enzymology* / Q000378:metabolism; D012697:Serine Endopeptidases / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D004792:Enzyme Precursors; D053491:Proteinase Inhibitory Proteins, Secretory; C109149:SPINT1 protein, human; D019859:Proto-Oncogene Proteins c-met; D012697:Serine Endopeptidases; C485595:matriptase
keywords: HAI-1; Kunitz-type protease inhibitor; hair follicles; matriptase; serine protease; zymogen activation