PMID- 29631978
OWN - NLM
STAT- MEDLINE
DCOM- 20190215
LR  - 20190215
IS  - 2050-0521 (Electronic)
IS  - 2050-0521 (Linking)
VI  - 6
IP  - 4
DP  - 2018 Oct
TI  - Suppression of Cavernosal Fibrosis in a Rat Model.
PG  - 572-582
LID - S2050-0521(18)30025-8 [pii]
LID - 10.1016/j.sxmr.2018.02.007 [doi]
AB  - INTRODUCTION: Cavernosal fibrosis is an important pathologic condition leading to 
      erectile dysfunction (ED). The etiologies of cavernosal fibrosis include aging, 
      diabetes mellitus, castration, cavernosal nerve injury during radical 
      prostatectomy, hypertension, and Peyronie disease. AIMS: To summarize published 
      studies investigating suppression of cavernosal fibrosis in rat models of ED of 
      various etiologies. METHODS: A literature search was conducted using PubMed. 
      Relevant studies were identified using search terms such as erectile dysfunction, 
      penis, fibrosis, and rat models. MAIN OUTCOME MEASURES: We reviewed 
      representative literature studies on the mechanisms and suppression of cavernosal 
      fibrosis in rat models of ED. RESULTS: The underlying mechanisms and potential 
      therapeutic strategies suggested thus far for cavernosal fibrosis in rat models 
      of ED were as follows. For age-related ED involving oxidative stress and tumor 
      growth factor-beta1 (TGF-beta1)-driven pathways such as RhoA-ROCK1-LIMK2-cofilin or 
      p42-44 and mitogen-activated protein kinase, proposed therapeutic strategies 
      included phosphodiesterase type 5 inhibitors (PDE5Is), kallikrein-kinin system 
      stimulators, and calorie restriction. For diabetes-related ED involving 
      angiotensin-II- and TGF-beta1-driven Smad and non-Smad pathways, TGF-beta1-Wnt10b, and 
      histone deacetylase (HDAC)-TGF-beta1 pathways, positive therapeutic results were 
      obtained with PDE5Is, TGF-beta1 antagonists, HDAC inhibitors, antioxidants, 
      sphingosine-1-phosphate receptor modulators (fingolimod), angiotensin-II 
      antagonists, stem cell therapy, and antidiabetic drugs. For cavernosal nerve 
      injury-associated ED involving TGF-beta1-driven pathways (Smad or 
      RhoA-ROCK1-LIMK2-cofilin), Sonic hedgehog signaling, angiotensin-II-Smad, and 
      HDAC4-TGF-beta1-Smad signaling triggered by cavernosal hypoxia, PDE5Is, 
      angiotensin-II antagonists, stem cell therapy, HDAC inhibitors, Sonic hedgehog 
      administration, ROCK inhibitors, and LIMK2 inhibitors have shown positive 
      results. For testosterone deficiency-associated ED, TGF-beta1-driven pathways were 
      found to be responsive to testosterone supplementation. For hypertensive ED, 
      positive therapeutic results were obtained with angiotensin-II antagonists. For 
      Peyronie disease involving TGF-beta1 or myostatin signaling, proposed therapeutic 
      strategies included intra-tunical injection of TGF-beta receptor inhibitors or 
      adipose tissue-derived stem cells and HDAC2 small hairpin RNA. CONCLUSION: 
      Several signaling pathways appear to be responsible for the development of 
      cavernosal fibrosis related to ED of various etiologies. Some therapeutic success 
      has been achieved in animal models, but further research focusing on 
      mechanism-specific targeted therapies is needed. Cho MC, Song WH, Paick J-S. 
      Suppression of Cavernosal Fibrosis in a Rat Model. Sex Med Rev 2018;6:572-582.
CI  - Copyright (c) 2018 International Society for Sexual Medicine. Published by Elsevier 
      Inc. All rights reserved.
FAU - Cho, Min Chul
AU  - Cho MC
AD  - Department of Urology, Seoul National University Boramae Medical Center, Seoul, 
      Korea.
FAU - Song, Won Hoon
AU  - Song WH
AD  - Department of Urology, Seoul National University College of Medicine, Seoul, 
      Korea.
FAU - Paick, Jae-Seung
AU  - Paick JS
AD  - Department of Urology, Seoul National University College of Medicine, Seoul, 
      Korea. Electronic address: jspaick@snu.ac.kr.
LA  - eng
PT  - Journal Article
PT  - Review
DEP - 20180407
PL  - Netherlands
TA  - Sex Med Rev
JT  - Sexual medicine reviews
JID - 101614773
SB  - IM
MH  - Animals
MH  - Disease Models, Animal
MH  - *Erectile Dysfunction
MH  - Fibrosis/drug therapy/prevention & control
MH  - Male
MH  - *Penile Diseases/drug therapy/prevention & control
MH  - Penis/*physiopathology
MH  - Rats
OTO - NOTNLM
OT  - Erectile Dysfunction
OT  - Fibrosis
OT  - Penis
OT  - Rat
EDAT- 2018/04/11 06:00
MHDA- 2019/02/16 06:00
CRDT- 2018/04/11 06:00
PHST- 2017/12/30 00:00 [received]
PHST- 2018/02/26 00:00 [revised]
PHST- 2018/02/27 00:00 [accepted]
PHST- 2018/04/11 06:00 [pubmed]
PHST- 2019/02/16 06:00 [medline]
PHST- 2018/04/11 06:00 [entrez]
AID - S2050-0521(18)30025-8 [pii]
AID - 10.1016/j.sxmr.2018.02.007 [doi]
PST - ppublish
SO  - Sex Med Rev. 2018 Oct;6(4):572-582. doi: 10.1016/j.sxmr.2018.02.007. Epub 2018 
      Apr 7.