Marked stimulation of growth and motility of human keratinocytes by hepatocyte growth factor.
Effect of hepatocyte growth factor (HGF) on normal human epidermal keratinocytes cultured under conditions of low Ca2+ (0.1 mM, growth-promoting condition) and physiological Ca2+ (1.8 mM, differentiation-promoting condition) was investigated. In low Ca2+, HGF markedly enhanced the migration of keratinocytes while it suppressed cell growth and DNA synthesis in a dose-dependent manner. In contrast, HGF enhanced the migration, cell growth, and DNA synthesis of keratinocytes cultured under conditions of physiological Ca2+. The maximal stimulation of DNA synthesis (2.4-fold stimulation) in physiological Ca2+ was seen at 2.5-5 ng/ml HGF and the stimulatory effect of HGF was suppressed by transforming growth factor-beta 1. Analysis of the HGF receptor using 125I-HGF as a ligand showed that human keratinocytes expressed a single class of specific, saturable receptor for HGF in both low and physiological Ca2+ conditions, exhibiting a Kd = 17.3 pM and approximately 690 binding sites/cell under physiological Ca2+. Thus, HGF is a potent factor which enhances growth and migration of normal human keratinocytes under conditions of physiological Ca2+. HGF may play an important role in epidermal tissue repair as it enhances both the migration and growth of keratinocytes.
Matsumoto
K
K
Department of Biology, Faculty of Science, Kyushu University, Fukuoka, Japan.
Hashimoto
K
K
Yoshikawa
K
K
Nakamura
T
T
D002118:Calcium / Q000494:pharmacology; D002455:Cell Division / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D002478:Cells, Cultured; D004247:DNA / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D006801:Humans; D015850:Interleukin-6 / Q000494:pharmacology*; D007457:Iodine Radioisotopes; D015603:Keratinocytes / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D011971:Receptors, Immunologic / Q000378:metabolism; D019947:Receptors, Interleukin-6
D015850:Interleukin-6; D007457:Iodine Radioisotopes; D011971:Receptors, Immunologic; D019947:Receptors, Interleukin-6; D004247:DNA; D002118:Calcium