Testosterone Rescues the De-Differentiation of Smooth Muscle Cells Through Serum Response Factor/Myocardin

Carolina Leimgruber, Amado A. Quintar, Nahuel Peinetti, María V. Scalerandi, Juan P. Nicola, Joseph M. Miano, Cristina A. Maldonado

Research output: Contribution to journalArticle

6 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)2806-2817
Number of pages12
JournalJournal of Cellular Physiology
Volume232
Issue number10
DOIs
StatePublished - Oct 2017
Externally publishedYes

ASJC Scopus subject areas

  • Physiology
  • Clinical Biochemistry
  • Cell Biology

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    Leimgruber, C., Quintar, A. A., Peinetti, N., Scalerandi, M. V., Nicola, J. P., Miano, J. M., & Maldonado, C. A. (2017). Testosterone Rescues the De-Differentiation of Smooth Muscle Cells Through Serum Response Factor/Myocardin. Journal of Cellular Physiology, 232(10), 2806-2817. https://doi.org/10.1002/jcp.25679