The parathyroid hormone-related protein (PTHrp), structurally similar to the parathyroid hormone (PTH) in its NH2- terminal part, was ﬁrst identiﬁed as a tumour-derived peptide responsible for a paraneoplastic syndrome known as humoral hypercalcemia of malignancy. The PTHrp gene is expressed not only in cancer but also in normal tissues during adult and/or fetal life, where it plays predominantly paracrine and/or autocrine roles. In the skin PTHrp produced by keratinocytes acts on ﬁbroblasts by complex cooperative circuits involving cytokines and growth factors. In this report, we studied the direct effects of synthetic PTHrp 1–40 on proliferation and collagen synthesis and matrix metalloproteinase-2 (MMP-2) activity in cultures of ﬁbroblasts isolated from normal human skin. Fibroblasts exposure to varying doses of PTHrp for 48h, signiﬁcantly and dose-dependently inhibited proliferation evaluated by [3 H]-thymidine incorporation into DNA. A dose-dependent stimulation of cAMP released into the medium was concomitantly observed. In contrast, PTHrp had no effect on collagen synthesis evaluated either by [3 H]-proline incorporation or by radioimmunoassay (RIA) of the carboxyterminal fragment of type I procollagen (PICP). MMP-2 activity, evaluated by quantitative zymographic analysis, was signiﬁcantly increased by PTHrp treatment at doses of 160 and 320nM. These ﬁndings indicate that PTHrp may play a role in normal dermal physiology by controlling both ﬁbroblast proliferation and extracellular matrix degradation.
|Titolo:||Effect of parathyroid hormone related protein on fibroblast proliferation and collagen metabolism in human skin|
|Appare nelle tipologie:||1.1 Articolo in rivista|