title: Testosterone Rescues the De-Differentiation of Smooth Muscle Cells Through Serum Response Factor/Myocardin.
abstract: Prostatic smooth muscle cells (pSMCs) differentiation is a key factor for prostatic homeostasis, with androgens exerting multiple effects on these cells. Here, we demonstrated that the myodifferentiator complex Srf/Myocd is up-regulated by testosterone in a dose-dependent manner in primary cultures of rat pSMCs, which was associated to the increase in Acta2, Cnn1, and Lmod1 expressions. Blocking Srf or Myocd by siRNAs inhibited the myodifferentiator effect of testosterone. While LPS led to a dedifferentiated phenotype in pSMCs, characterized by down-regulation of Srf/Myocd and smooth muscle cell (SMC)-restricted genes, endotoxin treatment on Myocd-overexpressing cells did not result in phenotypic alterations. Testosterone at a physiological dose was able to restore the muscular phenotype by normalizing Srf/Myocd expression in inflammation-induced dedifferentiated pSMCs. Moreover, the androgen reestablished the proliferation rate and IL-6 secretion increased by LPS. These results provide novel evidence regarding the myodifferentiating role of testosterone on SMCs by modulating Srf/Myocd. Thus, androgens preserve prostatic SMC phenotype, which is essential to maintain the normal structure and function of the prostate. J. Cell. Physiol. 232: 2806-2817, 2017. © 2016 Wiley Periodicals, Inc.
authors.affiliation: Centro de Microscopía Electrónica, Instituto de Investigaciones en Ciencias de la Salud (INICSA-CONICET), Facultad de Ciencias Médicas, Universidad Nacional de Córdoba, Córdoba, Argentina.
authors.forename: Carolina
authors.initials: C
authors.lastname: Leimgruber
authors.affiliation: Centro de Microscopía Electrónica, Instituto de Investigaciones en Ciencias de la Salud (INICSA-CONICET), Facultad de Ciencias Médicas, Universidad Nacional de Córdoba, Córdoba, Argentina.
authors.forename: Amado A
authors.initials: AA
authors.lastname: Quintar
authors.affiliation: Centro de Microscopía Electrónica, Instituto de Investigaciones en Ciencias de la Salud (INICSA-CONICET), Facultad de Ciencias Médicas, Universidad Nacional de Córdoba, Córdoba, Argentina.
authors.forename: Nahuel
authors.initials: N
authors.lastname: Peinetti
authors.affiliation: Centro de Microscopía Electrónica, Instituto de Investigaciones en Ciencias de la Salud (INICSA-CONICET), Facultad de Ciencias Médicas, Universidad Nacional de Córdoba, Córdoba, Argentina.
authors.forename: María V
authors.initials: MV
authors.lastname: Scalerandi
authors.affiliation: Centro de Investigaciones en Bioquímica Clínica e Inmunología (CIBICI-CONICET), Departamento de Bioquímica Clínica, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Córdoba, Argentina.
authors.forename: Juan P
authors.initials: JP
authors.lastname: Nicola
authors.affiliation: Aab Cardiovascular Research Institute, University of Rochester School of Medicine and Dentistry, Rochester, New York.
authors.forename: Joseph M
authors.initials: JM
authors.lastname: Miano
authors.affiliation: Centro de Microscopía Electrónica, Instituto de Investigaciones en Ciencias de la Salud (INICSA-CONICET), Facultad de Ciencias Médicas, Universidad Nacional de Córdoba, Córdoba, Argentina.
authors.forename: Cristina A
authors.initials: CA
authors.lastname: Maldonado
mesh_terms: D000199:Actins / Q000378:metabolism; D000818:Animals; D002135:Calcium-Binding Proteins / Q000378:metabolism; D054337:Cell Dedifferentiation / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D015850:Interleukin-6 / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D008840:Microfilament Proteins / Q000378:metabolism; D032389:Myocytes, Smooth Muscle / Q000187:drug effects* / Q000378:metabolism; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D010641:Phenotype; D011467:Prostate; D034622:RNA Interference; D017208:Rats, Wistar; D015398:Signal Transduction / Q000187:drug effects; D013739:Testosterone / Q000494:pharmacology*; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014162:Transfection; D000096985:Calponins; D000099251:Myocardin
chemical_list: D000199:Actins; D002135:Calcium-Binding Proteins; D015850:Interleukin-6; D008070:Lipopolysaccharides; D008840:Microfilament Proteins; D009687:Nuclear Proteins; D013739:Testosterone; D015534:Trans-Activators; D014157:Transcription Factors; D000096985:Calponins; D000099251:Myocardin; C000620714:serum response factor, rat; C498862:Acta2 protein, rat