Silencing myostatin increases area fraction of smooth muscle in the corpus cavernosum of pigs

Abstract

Myostatin (MSTN), an inhibitor of skeletal muscle growth, is also expressed in penile smooth muscle; however, it is unclear whether MSTN plays an inhibitory role in penile smooth muscle growth. We investigated the role of MSTN in the smooth muscle of the penile corpus cavernosum of pigs using MSTN homozygous mutant knockout (KO) and wild type (WT) pigs (n = 4 in each group). The mean of area fraction (%) of smooth muscle in the penile corpus cavernosum was 65.9 % ± 1.79 in the KO and approximately 41.7 % ± 5.39 in the WT (P < 0.001). KO pigs showed significantly increased expression of smooth muscle-specific genes, including smooth muscle protein 22 (TAGLN) (6.62-fold), smooth muscle myosin heavy chain (MYH11) (2.41-fold), myocardin (MYOCD) (3.05-fold), and serum response factor (SRF) (4.95-fold), and decreased expression of vimentin (VIM) (1.36-fold). Immunofluorescence staining and Western blotting showed smooth muscle-specific expression of α-smooth muscle actin (SMA) and calponin was higher in KO pigs (P < 0.05) than in WT pigs. KO pigs had less fat deposition inside the corpus cavernosum, and showed downregulation of adiponectin (ADIPOQ) and fatty acid synthase (FASN) (2.5-fold and 1.9-fold loss, respectively). In vitro experiments showed MSTN interference promoted corporal smooth muscle cell growth and expression of smooth muscle-specific markers, whereas it downregulated the expression of fat-specific genes, ADIPOQ and FASN. MSTN inhibition could promote smooth muscle growth and decrease fat deposition in the corpus cavernosum. MSTN, thus, could be a possible target for the treatment of smooth muscle dystrophy-related disorders such as erectile dysfunction.