title: Matriptase regulates proliferation and early, but not terminal, differentiation of human keratinocytes.
abstract: Genetic defects in matriptase are linked to two congenital ichthyoses: autosomal recessive ichthyosis with hypotrichosis (ARIH, OMIM 610765) and ichthyosis, follicular atrophoderma, hypotrichosis, and hypohidrosis (IFAH, OMIM 602400). Mouse models with matriptase deficiency indicate an involvement of matriptase in suprabasal keratinocytes in the maintenance of the epidermal barrier. In contrast to what has been reported for mouse skin, we show that in human skin matriptase is primarily expressed in the basal and spinous keratinocytes, but not in the more differentiated keratinocytes of the granular layer. In addition, matriptase zymogen activation was predominantly detected in the basal cells. Furthermore, by using skin organotypic cultures as a model system to monitor the course of human epidermal differentiation, we found elevated matriptase zymogen activation during early stages of epidermal differentiation, coupled with a loss of matriptase expression in the late stages of this process. We also show here that matriptase deficiency in HaCaT cells modestly reduces cell proliferation and temporally affects calcium-induced expression of differentiation markers. These collective data suggest that, unlike mouse matriptase, human matriptase may be involved in the regulation of keratinocyte growth and early differentiation, rather than terminal differentiation, providing mechanistic insights into the pathology of the two congenital ichthyoses: ARIH and IFAH.
authors.affiliation: Greenebaum Cancer Center, University of Maryland, Baltimore, Maryland, USA; Graduate Program in Life Science, University of Maryland, Baltimore, Maryland, USA.
authors.forename: Ya-Wen
authors.initials: YW
authors.lastname: Chen
authors.affiliation: Department of Biochemistry, National Defense Medical Center, Taipei, Taiwan.
authors.forename: Jehng-Kang
authors.initials: JK
authors.lastname: Wang
authors.affiliation: Greenebaum Cancer Center, University of Maryland, Baltimore, Maryland, USA.
authors.forename: Fen-Pai
authors.initials: FP
authors.lastname: Chou
authors.affiliation: Department of Dermatology, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan.
authors.forename: Bai-Yao
authors.initials: BY
authors.lastname: Wu
authors.affiliation: Department of Biochemistry, National Defense Medical Center, Taipei, Taiwan.
authors.forename: Hui-Chung
authors.initials: HC
authors.lastname: Hsiao
authors.affiliation: Department of Biochemistry, National Defense Medical Center, Taipei, Taiwan.
authors.forename: Han
authors.initials: H
authors.lastname: Chiu
authors.affiliation: Greenebaum Cancer Center, University of Maryland, Baltimore, Maryland, USA.
authors.forename: Zhonghong
authors.initials: Z
authors.lastname: Xu
authors.affiliation: Department of Medicine, University of Illinois in Chicago, Chicago, Illinois, USA.
authors.forename: Adrienne N H
authors.initials: ANH
authors.lastname: Baksh
authors.affiliation: G/T Intern/Mentor Program, Wilde Lake High School, Columbia, Maryland, USA.
authors.forename: Galen
authors.initials: G
authors.lastname: Shi
authors.affiliation: Department of Pharmacology, University of Medicine and Dentistry of New Jersey-Robert Wood Johnson Medical School, Piscataway, New Jersey, USA.
authors.forename: Malvika
authors.initials: M
authors.lastname: Kaul
authors.affiliation: Lombardi Comprehensive Cancer Center, Georgetown University, Washington, DC, USA.
authors.forename: Robert
authors.initials: R
authors.lastname: Barndt
authors.affiliation: Department of Medicine, Division of Rheumatology, Immunology and Allergy, MedStar Georgetown University Hospital, Washington, DC, USA.
authors.forename: Victoria K
authors.initials: VK
authors.lastname: Shanmugam
authors.affiliation: Lombardi Comprehensive Cancer Center, Georgetown University, Washington, DC, USA.
authors.forename: Michael D
authors.initials: MD
authors.lastname: Johnson
authors.affiliation: Lombardi Comprehensive Cancer Center, Georgetown University, Washington, DC, USA. Electronic address: lincy@georgetown.edu.
authors.forename: Chen-Yong
authors.initials: CY
authors.lastname: Lin
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000502:physiology*; D002461:Cell Line, Transformed; D049109:Cell Proliferation; D000078404:Epidermal Cells; D064593:Heterografts; D006801:Humans; D007039:Hypotrichosis / Q000151:congenital* / Q000235:genetics / Q000473:pathology; D007057:Ichthyosis / Q000235:genetics* / Q000473:pathology; D015603:Keratinocytes / Q000166:cytology* / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D009924:Organ Culture Techniques; D061251:Primary Cell Culture; D012697:Serine Endopeptidases / Q000235:genetics*
chemical_list: D012697:Serine Endopeptidases; C485596:ST14 protein, human
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