Browsing by Subject "Adrenomedullin"

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    Adrenomedullin regulates club cell recovery following lung epithelial injury
    (Universidad de Murcia. Departamento de Biología Celular e Histología, 2016) García-Sanmartín, Josune; Larrayoz, Ignacio M.; Martínez, Alfredo
    The equilibrium between lung epithelium damage and recovery in the context of chronic injury is at the basis of numerous lung diseases, including lung cancer and COPD. Understanding the contribution of growth factors and other molecular intermediates to this crosstalk may help in devising new therapeutic approaches. To better understand the contribution of adrenomedullin (AM) to lung homeostasis, we built club cell-specific conditional knockout (KO) mice for AM and subjected them to naphthalene injury. Untreated KO mice had lower levels of club cell 10 KDa protein (CC10) immunoreactivity than their wild type (WT) littermates in both terminal and regular bronchioles. Naphthalene injury resulted in a rapid necrosis of club cells followed by a progressive recovery of the epithelium. Club cells proliferated at higher rates in the KO mice and at 21 days post-injury the club cell coverage of the main bronchioles was higher and more homogeneous than in the WT animals. In conclusion, the paracrine/autocrine influence of AM in club cells subtly modulates their proliferation and spreading kinetics during lung epithelium recovery.
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    Proadrenomedullin-derived peptides as autocrine-paracrine regulators of cell growth
    (F. Hernández y Juan F. Madrid. Universidad de Murcia: Departamento de Biología Celular e Histología, 2001) Belloni, A. S.; Albertin, G.; Forneris, M. L.; Nussdorfer, G. G.
    Proa dr e nomedullin (pADM )-d e ri ve d peptides, adrenomedullin (ADM) and pADM N-terminal 20 peptide (PAMP), are hypotensive peptides, which are expressed, along with their receptors, in several tissues and orga ns, the function of which they regulate by acting in an aut ocrin e-parac rin e mann er. Apart fr om th eir involvement in the regul ation of blood pressure and fluid and electro lyte homeostasis, pADM-deri ved peptides appear to playa role in the modulation of cell and tissue growth. Evid ence has bee n prov ided th at ADM: I) favors th e remodeling of cardiovascular system under path ologica l conditi ons, by exe rting an anti apoptotic effect on endotheli al cells and an antiproliferogeni c and antimi gratory acti on on vascul ar smooth-muscle ce lls durin g neo intimal hype rpl asia, and by dec reasin g proliferation and protein ynthesis of cardiac myoeytes and fibrobl asts. These last two effects are mediated by ca lc ito nin ge ne -re lated peptid e type 1 (CGRPI ) receptors coupled to the adenylate cycl ase (AC)/protein kin ase ( PK) A-d epe nd e nt casca de; 2) inhi bits prolife rati o n and e nh a nces apo pt osis of kidn ey mesa ngial ce lls, through the modul ation of mi togenac ti va ted PK (MAPK ) casca des; 3) stimul ates proliferation of adrenal zona glomerulosa ce lls, acting via CG RPl rece ptor coupl ed to the tyrosin e kinase - depend ent MAPK cascade, th e reby possibl y bein g involved in the maintenance and stimulation of adrenal growth ; 4) enhances proliferati on of skin and mucosa epitheli al ce lls and fibrobl asts, by ac ti va ting CGRP] receptor coupled to the AC/PKA signaling pathway; and 5) enh ances proli fe rati on of several tumor- ce ll lines through the activa ti on of the AC/PKA cascade, which suggests a pote nti a l role fo r ADM as promo te r of neopl asti c growth. The growth effects of PAMP have bee n fa r less investiga ted: findings indicate that this peptide, like ADM. enhances adrenal zona glomerulosa ce ll proliferation, and, in contrast with ADM, depresses DNA synthesis in some cancer-cell lines. Both pADMde ri ve d peptid es are th o ug ht to be invol ve d in embryoge nesis, such a contention being based on the demonstration of high pADM-gene expression during the crucial phases of organ growth and differenti ation.