Role of inhibiting LIM-kinase2 in improving erectile function through suppression of corporal fibrosis in a rat model of cavernous nerve injury.
- Author:
Juhyun PARK
1
;
Sung Yong CHO
1
;
Kwanjin PARK
2
;
Ji Sun CHAI
2
;
Hwancheol SON
1
;
Soo Woong KIM
2
;
Jae-Seung PAICK
2
;
Min Chul CHO
1
Author Information
- Publication Type:Journal Article
- Keywords: LIM kinase; erectile dysfunction; fibrosis; penis; prostatectomy
- MeSH: Animals; Cofilin 1/metabolism*; Electric Stimulation; Erectile Dysfunction/etiology*; Fibroblasts/pathology*; Fibrosis/drug therapy*; Lim Kinases/antagonists & inhibitors*; Male; Penile Diseases/drug therapy*; Penis/innervation*; Peripheral Nerve Injuries/pathology*; Phosphorylation; Rats; Rats, Sprague-Dawley; Signal Transduction/drug effects*; rho-Associated Kinases/genetics*
- From: Asian Journal of Andrology 2018;20(4):372-378
- CountryChina
- Language:English
- Abstract: We evaluated whether LIM-kinase 2 inhibitor (LIMK2i) could improve erectile function by suppressing corporal fibrosis through the normalization of the Rho-associated coiled-coil protein kinase 1 (ROCK1)/LIMK2/Cofilin pathway in a rat model of cavernous nerve crush injury (CNCI). Sixty 11-week-old male Sprague-Dawley rats were divided equally into five groups: sham surgery (S), CNCI (I), and CNCI treated with low-dose (L), medium-dose (M), and high-dose (H) LIMK2i. The L, M, and H groups were treated with a daily intraperitoneal injection of LIMK2i (2.5, 5.0, and 10.0 mg kg-1 body weight, respectively) for 1 week after surgery. The erectile response was assessed using electrostimulation at 1 week, postoperatively. Penile tissues were processed for Masson's trichrome staining, double immunofluorescence, and Western blot assay. Erectile responses in the H group improved compared with the I group, while the M group showed only partial improvement. A significantly decreased smooth muscle/collagen ratio and an increased content of fibroblasts positive for phospho-LIMK2 were noted in the I group. The M and H groups revealed significant improvements in histological alterations and the dysregulated LIMK2/Cofilin pathway, except for LIMK2 phosphorylation in the M group. The inhibition of LIMK2 did not affect the ROCK1 protein expression. The content of fibroblasts positive for phospho-LIMK2 in the H group returned to the level found in the S group, whereas it did not in the M group. However, the L group did not exhibit such improvements. Our data suggest that the inhibition of LIMK2, particularly with administration of 10.0 mg kg-1 body weight LIMK2i, can improve corporal fibrosis and erectile function by normalizing the LIMK2/Cofilin pathway.
