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| INVITRO PARACRINE REGULATION OF HUMAN KERATINOCYTE GROWTH BY FIBROBLAST-DERIVED INSULIN-LIKE GROWTH-FACTORS |
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| Author(s): BARRECA A, DELUCA M, DELMONTE P, BONDANZA S, DAMONTE G, CARIOLA G, DIMARCO E, GIORDANO G, CANCEDDA R, MINUTO F |
| Source: JOURNAL OF CELLULAR PHYSIOLOGY Volume: 151 Issue: 2 Pages: 262-268 Published: MAY 1992 |
| Times Cited: 92 References: 26 |
| Abstract: Human keratinocytes isolated from a skin biopsy and cultured in vitro on a feeder-layer of irradiated fibroblasts reconstitute a stratified squamous epithelium suitable for grafting onto patients suffering from large burn wounds. Since conditioned medium from 3T3-j2 cells can partially substitute for the intact feeder-layer, we studied the possible involvement of insulin-like growth factors acting in a paracrine fashion. IGFs were measured (after Sephadex G-50 gel-chromatography in acid conditions) in media conditioned by a feeder-layer of lethally irradiated 3T3-J2 fibroblasts on which keratinocytes were grown. Immunoreactive (IR) IGF-I, IGF-II, and IGF binding activity were present in the medium conditioned by the feeder-layer. The medium conditioned by keratinocytes showed nearly undetectable amounts of IR IGF-I and IGF-II, suggesting that keratinocytes are unable to synthesize IGFs peptides. Recombinant IGF-I and IGF-II, and conditioned medium from 3T3-J2 cells, caused a dose-dependent increase of H-3-thymydine incorporation in cultured keratinocytes. The stimulatory effect of IGF and of 3T3-J2 conditioned medium was inhibited by the MoAb Sm 1.2, which recognizes both IGF-I and IG-II but not insulin, and by the MoAb alpha-3, which is a specific antagonist of type-I IGF receptor. Fetal mouse-derived 3T3-J2 cells and adult human skin fibroblasts were equally able to sustain keratinocyte growth and in both cases addition of Sm 1.2 MoAb causes a 50% decrease in the keratinocyte number. When the non-IGF-producing BALB/c 3T3 cells were used as a feeder-layer, the keratinocytes number was similar to that observed with 3T3-J2 and with human fibroblasts plus the Sm 1.2 MoAb. IGF-I and IGF-II restored the BALB/c 3T3 growth promoting activity to the level of 3T3-J2 and of normal human fibroblasts. Our results suggest that fetal mouse 3T3-J2 and human fibroblasts synthesize IGF peptides, while keratinocytes do not. Fibroblast-derived IGFs stimulate keratinocyte growth in a paracrine fashion, suggesting their role in the regulation of keratinocyte proliferation of skin growth and in wound healing. |
| Document Type: Article |
| Language: English |
| Reprint Address: BARRECA, A (reprint author), UNIV GENOA, DISEM, CATTEDRE ENDOCRINOL & FISIOPATOL ENDOCRINA, I-16132 GENOA, ITALY |
Addresses:
1. IST NAZL RIC CANC, DIFFERENZIAMENTO CELLULARE LAB, I-16132 GENOA, ITALY |
| Publisher: WILEY-LISS, DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 |
| Subject Category: Cell Biology; Physiology |
| IDS Number: HR760 |
| ISSN: 0021-9541 |
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| | | | | | | | | Record from Web of Science® | | | | | | | | | |