Human skin keratinocytes and fibroblasts express adrenomedullin and its receptors, and adrenomedullin enhances their growth in vitro by stimulating proliferation and inhibiting apoptosis

  • Authors:
    • Giovanna Albertin
    • Gianni Carraro
    • Pier Paolo Parnigotto
    • Maria Teresa Conconi
    • Agnieszka Ziolkowska
    • Ludwik K. Malendowicz
    • Gastone G. Nussdorfer
  • View Affiliations

  • Published online on: May 1, 2003     https://doi.org/10.3892/ijmm.11.5.635
  • Pages: 635-639
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Abstract

Adrenomedullin (ADM) is a hypotensive peptide, which originates from the proteolytic cleavage of pro(p)ADM and acts via two subtypes of receptors, named L1-R (L1-R) and calcitonin-receptor-like receptor (CRLR). L1-R is selective for ADM depending on the expression of the subtype 1 or the subtypes 2 and 3 of a family of chaperones, called receptor-activity-modifying proteins (RAMPs). Compelling evidence indicates that ADM, in addition to regulating blood pressure and water and electrolyte balance, also exerts a major growth promoting action in several normal and neoplastic cells. Reverse transcription (RT)-polymerase chain reaction (PCR) allowed the detection of pADM, L1-R and CRLR mRNAs in cultured human skin keratinocytes and fibroblasts. RAMP1 and RAMP2 (but not RAMP3) mRNAs were present, but their level of expression was rather weak, thereby suggesting that L1-R is the main subtype of ADM receptor in both keratinocytes and fibroblasts. ADM concentration-dependently raised the proliferation rate and lowered the apoptotic rate of both keratinocytes and fibroblasts cultured in vitro, maximal effective concentration being 10−8 M. The effects of 10−8 M ADM was annulled by the putative ADM-receptor antagonist ADM22-52 (10−6 M). ADM22-52 also lowered basal proliferative activity of keratinocytes and fibroblasts, without affecting their apoptotic deletion rate. Taken together, these findings allow us to conclude that i) human skin keratinocytes and fibroblasts express ADM and its receptors; and ii) endogenous ADM system promotes the growth of keratinocytes and fibroblasts cultured in vitro, by enhancing their proliferative activity and lowering their apoptotic deletion.

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May 2003
Volume 11 Issue 5

Print ISSN: 1107-3756
Online ISSN:1791-244X

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Spandidos Publications style
Albertin G, Carraro G, Parnigotto PP, Conconi MT, Ziolkowska A, Malendowicz LK and Nussdorfer GG: Human skin keratinocytes and fibroblasts express adrenomedullin and its receptors, and adrenomedullin enhances their growth in vitro by stimulating proliferation and inhibiting apoptosis. Int J Mol Med 11: 635-639, 2003.
APA
Albertin, G., Carraro, G., Parnigotto, P.P., Conconi, M.T., Ziolkowska, A., Malendowicz, L.K., & Nussdorfer, G.G. (2003). Human skin keratinocytes and fibroblasts express adrenomedullin and its receptors, and adrenomedullin enhances their growth in vitro by stimulating proliferation and inhibiting apoptosis. International Journal of Molecular Medicine, 11, 635-639. https://doi.org/10.3892/ijmm.11.5.635
MLA
Albertin, G., Carraro, G., Parnigotto, P. P., Conconi, M. T., Ziolkowska, A., Malendowicz, L. K., Nussdorfer, G. G."Human skin keratinocytes and fibroblasts express adrenomedullin and its receptors, and adrenomedullin enhances their growth in vitro by stimulating proliferation and inhibiting apoptosis". International Journal of Molecular Medicine 11.5 (2003): 635-639.
Chicago
Albertin, G., Carraro, G., Parnigotto, P. P., Conconi, M. T., Ziolkowska, A., Malendowicz, L. K., Nussdorfer, G. G."Human skin keratinocytes and fibroblasts express adrenomedullin and its receptors, and adrenomedullin enhances their growth in vitro by stimulating proliferation and inhibiting apoptosis". International Journal of Molecular Medicine 11, no. 5 (2003): 635-639. https://doi.org/10.3892/ijmm.11.5.635