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- Terracio, Louis, et al.
(författare)
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Induction of platelet-derived growth factor receptor expression in smooth muscle cells and fibroblasts upon tissue culturing
- 1988
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Ingår i: Journal of Cell Biology. - 0021-9525. ; 107:5, s. 1947-1957
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Tidskriftsartikel (refereegranskat)abstract
- The expression of platelet-derived growth factor (PDGF) receptors in porcine uterus and human skin in situ, was compared with that of cultured primary cells isolated from the same tissues. PDGF receptor expression was examined by monoclonal antibodies specific for the B type PDGF receptor and by RNA/RNA in situ hybridization with a probe constructed from a cDNA clone encoding the B type PDGF receptor. In porcine uterus tissue both mRNA and the protein product for the PDGF receptor were detected in the endometrium; the myometrium, in contrast, contained much lower amounts. Moreover, freshly isolated myometrial cells were devoid of PDGF receptors. However, after 1 d in culture receptors appeared, and after 2 wk of culturing essentially all of the myometrial cells stained positively with the anti-PDGF receptor antibodies and contained PDGF receptor mRNA. Similarly, B type PDGF receptors were not detected in normal human skin, but fibroblast-like cells from explant cultures of human skin possessed PDGF receptors. When determined by immunoblotting, porcine uterus myometrial membranes contained approximately 20% of the PDGF receptor antigen compared with the amount found in endometrial membranes. In addition, PDGF stimulated the phosphorylation of a 175-kD component, most likely representing autophosphorylation of the B type PDGF receptor in endometrial membranes, whereas only a marginal phosphorylation was seen in myometrial membranes. Taken together, these results demonstrate that PDGF receptor expression varies in normal tissues and that fibroblasts and smooth muscle cells do not uniformly express the receptor in situ. Furthermore, fibroblasts and smooth muscle cells that are released from tissues are induced to express PDGF receptors in response to cell culturing. The data suggest that, in addition to the availability of the ligand, PDGF-mediated cell growth in vivo is dependent on factors regulating expression of the receptor.
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| 2. |
- Tingström, Anders, et al.
(författare)
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Regulation of fibroblast-mediated collagen gel contraction by platelet-derived growth factor, interleukin-1 alpha and transforming growth factor-beta 1
- 1992
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Ingår i: Journal of Cell Science. - 0021-9533. ; 102:2, s. 315-322
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Tidskriftsartikel (refereegranskat)abstract
- We have examined the effects of three macrophagederived cytokines, platelet-derived growth factor (PDGF), transforming growth factor-01 (TGF-01) and interleukin-1 a (IL-la) on the contraction of collagen type I gels populated by human foreskin fibroblasts. Contraction was quantified as loss in gel weight. Both PDGF-AA and PDGF-BB were found to induce a rapid collagen-gel contraction. TGF-/J1 also stimulated gel contraction but with a delayed onset and at a slower rate than the PDGF-stimulated contraction. Rabbit polyclonal IgGs recognizing PDGF-AA and PDGF-BB, respectively, specifically inhibited the effects of the corresponding PDGF Lsoforms. However, the stimulatory effect of TGF-/S1 was not affected by any of the anti-PDGF antibodies. The ability of PDGF to stimulate contraction became less pronounced in collagen gel cultures grown in the absence of growth factors over periods of several days. Under the same conditions, the stimulatory effect of TGF-/J1 was not reduced. The reduced response to PDGF may be due to reduced tension on fibroblasts growing in collagen gels, since fibroblasts on free-floating gels showed a marked reduction in PDGF-BB-induced PDGF ^-receptor aggregates when compared to fibroblasts on attached collagen gels. LL-1 a inhibited initial collagen gel contraction, and at later stages induced a visible degradation of the collagen gels, presumably due to the generation of collagenase activity. The combination of IL-la and PDGF-BB stimulated initial collagen gel contraction, although less effectively than PDGF-BB alone. At later stages, collagen gel degradation was stimulated by this combination of cytokines. In contrast, the combination of IL-la and TGF-/51 did not stimulate collagen gel contraction, or any visible collagen gel degradation. Our data suggest that fibroblast-mediated collagen gel contraction can be modulated by cytokines via different mechanisms. Our data are of importance in the understanding of the modulatory roles of cytokines in connective tissue cell activities in inflammatory processes, such as wound healing.
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