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Silencing Histone Deacetylase 7 Alleviates Transforming Growth Factor-?1-Induced Profibrotic Responses in Fibroblasts Derived from Peyronie's Plaque.


ABSTRACT: PURPOSE:Epigenetic modifications, such as histone acetylation/deacetylation and DNA methylation, play a crucial role in the pathogenesis of inflammatory disorders and fibrotic diseases. The aim of this study was to study the differential gene expression of histone deacetylases (HDACs) in fibroblasts isolated from plaque tissue of Peyronie's disease (PD) or normal tunica albuginea (TA) and to examine the anti-fibrotic effect of small interfering RNA (siRNA)-mediated silencing of HDAC7 in fibroblasts derived from human PD plaque. MATERIALS AND METHODS:For differential gene expression study, we performed reverse-transcriptase polymerase chain reaction for HDAC isoforms (1-11) in fibroblasts isolated from PD plaque or normal TA. Fibroblasts isolated from PD plaque were pretreated with HDAC7 siRNA (100 pmol) and then stimulated with transforming growth factor-?1 (TGF-?1, 10 ng/mL). Protein was extracted from treated fibroblasts for Western blotting. We also performed immunocytochemistry to detect the expression of extracellular matrix proteins and to examine the effect of HDAC2 siRNA on the TGF-?1-induced nuclear translocation of Smad2/3 and myofibroblastic differentiation. RESULTS:The mRNA expression of HDAC2, 3, 4, 5, 7, 8, 10, and 11 was higher in fibroblasts isolated from PD plaque than in fibroblasts isolated from normal TA tissue. Knockdown of HDAC7 in PD fibroblasts inhibited TGF-?1-induced nuclear shuttle of Smad2 and Smad3, transdifferentiation of fibroblasts into myofibroblasts, and abrogated TGF-?1-induced production of extracellular matrix protein. CONCLUSIONS:These findings suggest that specific inhibition of HDAC7 with RNA interference may represent a promising epigenetic therapy for PD.

SUBMITTER: Kang DH 

PROVIDER: S-EPMC5924955 | biostudies-literature | 2018 May

REPOSITORIES: biostudies-literature

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Silencing Histone Deacetylase 7 Alleviates Transforming Growth Factor-β1-Induced Profibrotic Responses in Fibroblasts Derived from Peyronie's Plaque.

Kang Dong Hyuk DH   Yin Guo Nan GN   Choi Min Ji MJ   Song Kang Moon KM   Ghatak Kalyan K   Minh Nguyen Nhat NN   Kwon Mi Hye MH   Seong Do Hwan DH   Ryu Ji Kan JK   Suh Jun Kyu JK  

The world journal of men's health 20180501 2


<h4>Purpose</h4>Epigenetic modifications, such as histone acetylation/deacetylation and DNA methylation, play a crucial role in the pathogenesis of inflammatory disorders and fibrotic diseases. The aim of this study was to study the differential gene expression of histone deacetylases (HDACs) in fibroblasts isolated from plaque tissue of Peyronie's disease (PD) or normal tunica albuginea (TA) and to examine the anti-fibrotic effect of small interfering RNA (siRNA)-mediated silencing of HDAC7 in  ...[more]

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