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Kang DH, Yin GN, Choi MJ, et al. Silencing Histone Deacetylase 7 Alleviates Transforming Growth Factor-β1-Induced Profibrotic Responses in Fibroblasts Derived from Peyronie's Plaque. World J Mens Health. 2018;36(2):139-146doi: 10.5534/wjmh.170005.
Kang, D. H., Yin, G. N., Choi, M. J., Song, K. M., Ghatak, K., Minh, N. N., Kwon, M. H., Seong, D. H., Ryu, J. K., & Suh, J. K. (2018). Silencing Histone Deacetylase 7 Alleviates Transforming Growth Factor-β1-Induced Profibrotic Responses in Fibroblasts Derived from Peyronie's Plaque. The world journal of men's health, 36(2), 139-146. https://doi.org/10.5534/wjmh.170005
Kang, Dong Hyuk, et al. "Silencing Histone Deacetylase 7 Alleviates Transforming Growth Factor-β1-Induced Profibrotic Responses in Fibroblasts Derived from Peyronie's Plaque." The world journal of men's health vol. 36,2 (2018): 139-146. doi: https://doi.org/10.5534/wjmh.170005
Kang DH, Yin GN, Choi MJ, Song KM, Ghatak K, Minh NN, Kwon MH, Seong DH, Ryu JK, Suh JK. Silencing Histone Deacetylase 7 Alleviates Transforming Growth Factor-β1-Induced Profibrotic Responses in Fibroblasts Derived from Peyronie's Plaque. World J Mens Health. 2018 May;36(2):139-146. doi: 10.5534/wjmh.170005. PMID: 29706035; PMCID: PMC5924955.
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World J Mens Health. 2018 May;36(2):139-146. doi: 10.5534/wjmh.170005.

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

The world journal of men's health

Dong Hyuk Kang, Guo Nan Yin, Min Ji Choi, Kang Moon Song, Kalyan Ghatak, Nguyen Nhat Minh, Mi Hye Kwon, Do Hwan Seong, Ji Kan Ryu, Jun Kyu Suh

Affiliations

  1. National Research Center for Sexual Medicine, Inha University School of Medicine, Incheon, Korea.
  2. Department of Urology, Inha University School of Medicine, Incheon, Korea.
  3. Inha Research Institute for Medical Sciences, Inha University School of Medicine, Incheon, Korea. [email protected].
  4. Department of Urology, Inha University School of Medicine, Incheon, Korea. [email protected].

PMID: 29706035 PMCID: PMC5924955 DOI: 10.5534/wjmh.170005

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-β1 (TGF-β1, 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-β1-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-β1-induced nuclear shuttle of Smad2 and Smad3, transdifferentiation of fibroblasts into myofibroblasts, and abrogated TGF-β1-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.

Copyright © 2018 Korean Society for Sexual Medicine and Andrology.

Keywords: Extracellular matrix; Fibrosis; Histone deacetylases; Penile induration; Transforming growth factors

Conflict of interest statement

The authors have no potential conflicts of interest to disclose.

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