title: Phenotypic modulation of corpus cavernosum smooth muscle cells in a rat model of cavernous neurectomy.
abstract: BACKGROUND
  Patients undergoing radical prostatectomy (RP) are at high risk for erectile dysfunction (ED) due to potential cavernous nerve (CN) damage during surgery. Penile hypoxia after RP is thought to significantly contribute to ED pathogenesis.
  
  
  OBJECTIVE
  We previously showed that corpora cavernosum smooth muscle cells (CCSMCs) undergo phenotypic modulation under hypoxic conditions in vitro. Here, we studied such changes in an in vivo post-RP ED model by investigating CCSMCs in bilateral cavernous neurectomy (BCN) rats.
  
  
  METHODS
  Sprague-Dawley rats underwent sham (n = 12) or BCN (n = 12) surgery. After 12 weeks, they were injected with apomorphine to determine erectile function. The penile tissues were harvested and assessed for fibrosis using Masson trichrome staining and for molecular markers of phenotypic modulation using immunohistochemistry and western blotting. CCSMC morphological structure was evaluated by hematoxylin-eosin (H&E) staining and transmission electron microscopy (TEM).
  
  
  RESULTS
  Erectile function was significantly lower in BCN rats than in sham rats. BCN increased hypoxia-inducible factor-1α and collagen protein expression in corpora cavernous tissue. H&E staining and TEM showed that CCSMCs in BCN rats underwent hypertrophy and showed rough endoplasmic reticulum formation. The expression of CCSMC phenotypic markers, such as smooth muscle α-actin, smooth muscle myosin heavy chain, and desmin, was markedly lower, whereas vimentin protein expression was significantly higher in BCN rats than in control rats.
  
  
  CONCLUSIONS
  CCSMCs undergo phenotype modulation in rats with cavernous neurectomy. The results have unveiled physiological transformations that occur at the cellular and molecular levels and have helped characterize CN injury-induced ED.
authors.affiliation: Department of Urology, The Second Affiliated Hospital, Zhejiang Chinese Medical University, Hangzhou, China.
authors.forename: Fan
authors.initials: F
authors.lastname: Yang
authors.affiliation: Department of Urology, The Second Affiliated Hospital, Zhejiang Chinese Medical University, Hangzhou, China.
authors.forename: Jian F
authors.initials: JF
authors.lastname: Zhao
authors.affiliation: Laboratory Animal Research Center, Zhejiang Chinese Medical University, Hangzhou, China.
authors.forename: Qi Y
authors.initials: QY
authors.lastname: Shou
authors.affiliation: Department of Urology, The Second Affiliated Hospital, Zhejiang Chinese Medical University, Hangzhou, China.
authors.forename: Xiao J
authors.initials: XJ
authors.lastname: Huang
authors.affiliation: Department of Urology, The Second Affiliated Hospital, Zhejiang Chinese Medical University, Hangzhou, China.
authors.forename: Gang
authors.initials: G
authors.lastname: Chen
authors.affiliation: Department of Urology, The Second Affiliated Hospital, Zhejiang Chinese Medical University, Hangzhou, China.
authors.forename: Ke B
authors.initials: KB
authors.lastname: Yang
authors.affiliation: Department of Urology, The Second Affiliated Hospital, Zhejiang Chinese Medical University, Hangzhou, China.
authors.forename: Shi G
authors.initials: SG
authors.lastname: Zhang
authors.affiliation: Department of Urology, The Second Affiliated Hospital, Zhejiang Chinese Medical University, Hangzhou, China; Andrology Laboratory on Integration of Chinese and Western Medicine, Zhejiang provincial Key Laboratory of Traditional Chinese Medicine, Hangzhou, China.
authors.forename: Bo D
authors.initials: BD
authors.lastname: Lv
authors.affiliation: Central Laboratory, The Second Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou, China; Andrology Laboratory on Integration of Chinese and Western Medicine, Zhejiang provincial Key Laboratory of Traditional Chinese Medicine, Hangzhou, China.
authors.forename: Hui Y
authors.initials: HY
authors.lastname: Fu
mesh_terms: D000818:Animals; D007172:Erectile Dysfunction / Q000209:etiology / Q000473:pathology*; D024022:Fibrillar Collagens / Q000378:metabolism; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism; D008297:Male; D032389:Myocytes, Smooth Muscle / Q000502:physiology*; D010413:Penis / Q000294:innervation / Q000473:pathology*; D059348:Peripheral Nerve Injuries / Q000209:etiology / Q000473:pathology*; D011468:Prostatectomy / Q000009:adverse effects*; D017207:Rats, Sprague-Dawley
chemical_list: D024022:Fibrillar Collagens; C497444:Hif1a protein, rat; D051795:Hypoxia-Inducible Factor 1, alpha Subunit