Rosiglitazone inhibits proliferation, motility, and matrix metalloproteinase production in keratinocytes

被引:47
作者
Bhagavathula, N
Nerusu, KC
Lal, A
Ellis, CN
Chittiboyina, A
Avery, MA
Ho, CI
Benson, SC
Pershadsingh, HA
Kurtz, TW
Varani, J
机构
[1] Univ Michigan, Dept Pathol, Sch Med, Ann Arbor, MI 48109 USA
[2] Univ Michigan, Dept Dermatol, Sch Med, Ann Arbor, MI 48109 USA
[3] Univ Mississippi, Dept Med Chem, University, MS 38677 USA
[4] Calif State Univ Hayward, Dept Biol Sci, Hayward, CA 94542 USA
[5] Kern Med Ctr, Dept Family Med, Irvine, CA USA
[6] Univ Calif Irvine, Dept Family Med, Irvine, CA USA
[7] Bethesda Pharmaceut Inc, Bakersfield, CA USA
[8] Univ Calif San Francisco, Dept Lab Med, San Francisco, CA 94143 USA
关键词
hyperplasia; psoriasis; peroxisome proliferator-activated receptor-gamma (PPAR-gamma); epidermal growth factor; thiazolinedione;
D O I
10.1046/j.0022-202X.2003.22111.x
中图分类号
R75 [皮肤病学与性病学];
学科分类号
100206 ;
摘要
This study was undertaken to evaluate the effects of thiazolidinediones (TZD) on keratinocyte proliferation, motility, and matrix metalloproteinase (MMP) production. Rosiglitazone (a potent TZD) inhibited both proliferation and motility as well as elaboration of MMP-1 and MMP-9. Inhibition was obtained with keratinocytes in monolayer culture and human skin in organ culture. There were significant concentration-response differences in sensitivity of the three keratinocyte responses to treatment with rosiglitazone. In contrast to keratinocytes, dermal fibroblasts were resistant to the effects of rosiglitazone. Treatment of keratinocytes with rosiglitazone did not suppress epidermal growth factor receptor autophosphorylation, but inhibited signaling through the extracellular regulated kinase mitogen-activated protein kinase pathway without a concomitant effect on pathways that lead to c-jun activation. Pioglitazone, another TZD, also suppressed keratinocyte proliferation, although it was less effective than rosiglitazone. An experimental TZD (BP-1107) inhibited keratinocyte proliferation at a much lower concentration than either rosiglitazone or pioglitazone. Because enhanced keratinocyte motility and increased MMP production as well as increased keratinocyte proliferation are thought to contribute to the phenotype of psoriatic lesional skin, we propose that interference with these keratinocyte responses contributes to the previously reported antipsoriatic activity of TZD.
引用
收藏
页码:130 / 139
页数:10
相关论文
共 57 条
  • [1] CELL-MIGRATION IS ESSENTIAL FOR SUSTAINED GROWTH OF KERATINOCYTE COLONIES - THE ROLES OF TRANSFORMING GROWTH FACTOR-ALPHA AND EPIDERMAL GROWTH-FACTOR
    BARRANDON, Y
    GREEN, H
    [J]. CELL, 1987, 50 (07) : 1131 - 1137
  • [2] NORMAL KERATINIZATION IN A SPONTANEOUSLY IMMORTALIZED ANEUPLOID HUMAN KERATINOCYTE CELL-LINE
    BOUKAMP, P
    PETRUSSEVSKA, RT
    BREITKREUTZ, D
    HORNUNG, J
    MARKHAM, A
    FUSENIG, NE
    [J]. JOURNAL OF CELL BIOLOGY, 1988, 106 (03) : 761 - 771
  • [3] Independent role of p38 and ERK1/2 mitogen-activated kinases in the upregulation of matrix metalloproteinase-1
    Brauchle, M
    Glück, D
    Di Padova, F
    Han, JH
    Gram, H
    [J]. EXPERIMENTAL CELL RESEARCH, 2000, 258 (01) : 135 - 144
  • [4] Nuclear translocation of p42/p44 mitogen-activated protein kinase is required for growth factor-induced gene expression and cell cycle entry
    Brunet, A
    Roux, D
    Lenormand, P
    Dowd, S
    Keyse, S
    Pouysségur, J
    [J]. EMBO JOURNAL, 1999, 18 (03) : 664 - 674
  • [5] EPIDERMAL GROWTH-FACTOR RECEPTOR-MEDIATED CELL MOTILITY - PHOSPHOLIPASE-C ACTIVITY IS REQUIRED, BUT MITOGEN-ACTIVATED PROTEIN-KINASE ACTIVITY IS NOT SUFFICIENT FOR INDUCED CELL-MOVEMENT
    CHEN, P
    XIE, H
    SEKAR, MC
    GUPTA, K
    WELLS, A
    [J]. JOURNAL OF CELL BIOLOGY, 1994, 127 (03) : 847 - 857
  • [6] Decreased extracellular-signal-regulated kinase and increased stress-activated MAP kinase activities in aged human skin in vivo
    Chung, JH
    Kang, S
    Varani, J
    Lin, J
    Fisher, GJ
    Voorhees, JJ
    [J]. JOURNAL OF INVESTIGATIVE DERMATOLOGY, 2000, 115 (02) : 177 - 182
  • [7] COOK PW, 1992, CANCER RES, V52, P3224
  • [8] Transgenic expression of the human amphiregulin gene induces a psoriasis-like phenotype
    Cook, PW
    Piepkorn, M
    Clegg, CH
    Plowman, GD
    DeMay, JM
    Brown, JR
    Pittelkow, MR
    [J]. JOURNAL OF CLINICAL INVESTIGATION, 1997, 100 (09) : 2286 - 2294
  • [9] OVEREXPRESSION OF TRANSFORMING GROWTH FACTOR-ALPHA IN PSORIATIC EPIDERMIS
    ELDER, JT
    FISHER, GJ
    LINDQUIST, PB
    BENNETT, GL
    PITTELKOW, MR
    COFFEY, RJ
    ELLINGSWORTH, L
    DERYNCK, R
    VOORHEES, JJ
    [J]. SCIENCE, 1989, 243 (4892) : 811 - 814
  • [10] Troglitazone improves psoriasis and normalizes models of proliferative skin disease -: Ligands for peroxisome proliferator-activated receptor-γ inhibit keratinocyte proliferation
    Ellis, CN
    Varani, J
    Fisher, GJ
    Zeigler, ME
    Pershadsingh, HA
    Benson, SC
    Chi, YQ
    Kurtz, TW
    [J]. ARCHIVES OF DERMATOLOGY, 2000, 136 (05) : 609 - 616