Human skin keratinocytes and fibroblasts express adrenomedullin and its receptors, and adrenomedullin enhances their growth in vitro by stimulating proliferation and inhibiting apoptosis
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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Document Type: Research Article
Affiliations: Department of Human Anatomy and Physiology (Section of Anatomy), University of Padua, I-35121 Padua, Italy
Publication date: May 1, 2003
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- The International Journal of Molecular Medicine is a monthly, peer-reviewed journal devoted to the publication of high quality studies related to the molecular mechanisms of human disease. The journal welcomes research on all aspects of molecular and clinical research, ranging from biochemistry to immunology, pathology, genetics, human genomics, microbiology, molecular pathogenesis, molecular cardiology, molecular surgery and molecular psychology.
The International Journal of Molecular Medicine aims to provide an insight for researchers within the community in regard to developing molecular tools and identifying molecular targets for the diagnosis and treatment of a diverse number of human diseases.
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