Involvement of Rho-Kinase/LIM Kinase/Cofilin Signaling Pathway in Corporal Fibrosis after Cavernous Nerve Injury in Male Rats.

Abstract

INTRODUCTION:

The molecular mechanism of corporal fibrosis leading to erectile dysfunction (ED) following cavernous nerve (CN) injury is poorly understood.

AIM:

To determine whether the LIMK2/cofilin pathway, the downstream effectors of ROCK1, was involved in ED and corporal fibrosis following bilateral CN injury in male rats.

METHODS:

Forty-eight 10-week-old male Sprague-Dawley rats were equally divided into three groups: sham surgery (S); bilateral CN crush injury (I); and bilateral CN resection (R). Within each groups, two subgroups were analyzed at 1 and 4 weeks postoperatively.

MAIN OUTCOME MEASURES:

Electrostimulation was performed to assess erectile function by the ratio of maximal intracavernous pressure to mean arterial pressure (ICP/MAP) and areas under the ICP curve to MAP (AUC/MAP). Penile tissue was processed for Masson's trichrome staining, Western blot (ROCK1, total LIMK2, phospho-LIMK2, total cofilin, phospho-cofilin), immunohistochemistry (alpha-SM actin [α-SMA]), and double immunofluorescent staining (ROCK1, phospho-LIMK2, vimentin).

RESULTS:

At each time point, both I and R groups showed a significantly lower percent of ICP/MAP and AUC, and decreased SM cell/collagen ratio and expression of α-SMA than S group. Densitometry revealed a significantly higher expression of ROCK1 in I and R groups compared with S group at all time points. The LIMK2 phosphorylation in I and R groups significantly increased at 1 week, but not at 4 weeks. The cofilin phosphorylation in R group significantly increased to that in S group starting at 1 week, while that in I group was increased significantly at 4 weeks. The double immunofluorescent staining noted that coexpression of vimentin with ROCK1 or phospho-LIMK2 in I and R groups was significantly increased mainly in the subtunical area at 1 week but not at 4 weeks.

CONCLUSIONS:

The ROCK1/LIMK2/cofilin pathway may be involved in ED related to corporal fibrosis, and it appears to be functional particularly in the early period after CN injury.

• Authors: Sang Hoon Song, Kwanjin Park, Soo Woong Kim, Jae-Seung Paick, Min Chul Cho
• Journal: The journal of sexual medicine (J Sex Med) Vol. 12 Issue 7 Pg. 1522-32 (Jul 2015) ISSN: 1743-6109 [Electronic] Netherlands
• PMID: 25923835 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2015 International Society for Sexual Medicine.

Chemical References

• Cfl1 protein, rat
• Cofilin 1
• Lim Kinases
• ROCK1 protein, human
• rho-Associated Kinases

Topics

• Animals
• Blotting, Western
• Cofilin 1 (metabolism)
• Disease Models, Animal
• Erectile Dysfunction (enzymology)
• Fibrosis (enzymology)
• Lim Kinases (metabolism)
• Male
• Nerve Crush
• Penis (blood supply, innervation, pathology)
• Phosphorylation
• Rats
• Rats, Sprague-Dawley
• Recovery of Function
• Signal Transduction
• rho-Associated Kinases (antagonists & inhibitors, metabolism)