Caveolin-1 and -2 expression is differentially regulated in cultured keratinocytes and within the regenerating epidermis of cutaneous wounds.
Keratinocyte growth factor (KGF) and its receptor are involved in various types of epithelial repair processes. To gain insight into the molecular mechanisms of KGF action in the healing skin wound, we searched for genes which are regulated by this factor in cultured keratinocytes. Using the PCR-select technology we constructed a subtractive cDNA library. One of the KGF-regulated genes that we identified was shown to encode caveolin-1, a major component of caveolar membranes. Caveolin-1 is involved in a wide variety of cellular processes, particularly in the regulation of various signal transduction pathways. Caveolin-1 mRNA levels increased in cultured keratinocytes after KGF treatment. By in situ hybridization and immunohistochemistry we found a strong expression of caveolin-1 in the KGF-responsive basal keratinocytes of the epidermis and the hyperproliferative epithelium of the wound as well as in endothelial cells and in other cells of the granulation tissue. In 13-day wounds expression of caveolin-1 mRNA was restricted to the regenerated dermis. In addition to caveolin-1, the mRNA expression of caveolin-2, a second member of the caveolin family, was also induced in keratinocytes after stimulation with KGF but also with other growth factors and cytokines. In contrast to caveolin-1, caveolin-2 protein was expressed in all layers of the normal epidermis and in the suprabasal layers of the hyperproliferative wound epithelium. These results demonstrate a differential expression of caveolin-1 and -2 in proliferating versus differentiating keratinocytes.
Max-Planck-Institute of Biochemistry, Martinsried, Germany.
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MG
Gassmann
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S
Werner
D000818:Animals; D051242:Caveolin 1; D051243:Caveolin 2; D022461:Caveolins; D002460:Cell Line; D004815:Epidermal Growth Factor / Q000494:pharmacology; D004817:Epidermis / Q000502:physiology* / Q000503:physiopathology; D051526:Fibroblast Growth Factor 10; D051523:Fibroblast Growth Factor 7; D005346:Fibroblast Growth Factors; D019084:Fluorescent Antibody Technique, Indirect; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology*; D015723:Gene Library; D006133:Growth Substances / Q000494:pharmacology / Q000502:physiology*; D006801:Humans; D015603:Keratinocytes / Q000502:physiology*; D008565:Membrane Proteins / Q000032:analysis / Q000235:genetics*; D051379:Mice; D008807:Mice, Inbred BALB C; D012333:RNA, Messenger / Q000235:genetics; D012867:Skin / Q000293:injuries; D014158:Transcription, Genetic; D016212:Transforming Growth Factor beta / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D014945:Wound Healing / Q000187:drug effects / Q000235:genetics*
C495540:CAV1 protein, human; C495541:Cav1 protein, mouse; D051242:Caveolin 1; D051243:Caveolin 2; D022461:Caveolins; C496453:FGF7 protein, human; C496454:Fgf7 protein, mouse; D051526:Fibroblast Growth Factor 10; D006133:Growth Substances; D008565:Membrane Proteins; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta; D014409:Tumor Necrosis Factor-alpha; D051523:Fibroblast Growth Factor 7; D005346:Fibroblast Growth Factors; D004815:Epidermal Growth Factor