We found a match
Your institution may have rights to this item. Sign in to continue.
- Title
Silencing histone deacetylase 2 using small hairpin RNA induces regression of fibrotic plaque in a rat model of Peyronie's disease.
- Authors
Kwon, Ki‐Dong; Choi, Min Ji; Park, Jin‐Mi; Song, Kang‐Moon; Kwon, Mi‐Hye; Batbold, Dulguun; Yin, Guo Nan; Kim, Woo Jean; Ryu, Ji‐Kan; Suh, Jun‐Kyu
- Abstract
Objectives To examine the therapeutic effect of adenovirus encoding histone deacetylase 2 ( HDAC2) small hairpin RNA ( Ad-HDAC2 shRNA) in a rat model of Peyronie's disease ( PD) and to determine the mechanisms by which HDAC2 knockdown ameliorates fibrotic responses in primary fibroblasts derived from human PD plaque. Materials and Methods Rats were distributed into four groups ( n = 6 per group): age-matched controls without treatment; rats in which PD has been induced ( PD rats) without treatment; PD rats receiving a single injection of control adenovirus encoding scrambled small hairpin RNA (Ad-shRNA) (day 15; 1 × 108 pfu/0.1 mL phosphate-buffered saline [ PBS]); and PD rats receiving a single injection of Ad-HDAC2 shRNA (day 15; 1 × 108 pfu/0.1 mL PBS) into the lesion. PD-like plaque was induced by repeated intratunical injections of 100 μL each of human fibrin and thrombin solutions on days 0 and 5. On day 30, the penis was harvested for histological examination. Fibroblasts isolated from human PD plaque were pretreated with HDAC2 small interfering (si) RNA (100 pmoL) and then stimulated with transforming growth factor ( TGF)-β1 (10 ng/mL) to determine hydroxyproline levels, procollagen mRNA, apoptosis and protein expression of poly( ADP-ribose) polymerase 1 ( PARP1) and cyclin D1. Results We observed that Ad-HDAC2 shRNA decreased inflammatory cell infiltration, reduced transnuclear expression of phospho- Smad3 and regressed fibrotic plaque of the tunica albuginea in PD rats in vivo. siRNA-mediated silencing of HDAC2 significantly decreased the TGF-β1-induced transdifferentiation of fibroblasts into myofibroblasts and collagen production, and induced apoptosis by downregulating the expression of PARP1, and decreased the expression of cyclin D1 (a positive cell-cycle regulator) in primary cultured fibroblasts derived from human PD plaque in vitro. Conclusion Specific inhibition of HDAC2 with RNA interference may represent a novel targeted therapy for PD.
- Subjects
GENE silencing; REGRESSION analysis; PENILE induration; LABORATORY rats; FIBROBLASTS; ADENOVIRUSES
- Publication
BJU International, 2014, Vol 114, Issue 6, p926
- ISSN
1464-4096
- Publication type
Article
- DOI
10.1111/bju.12812