PloS one, 2019-03, Vol.14 (3), p.e0213586-e0213586
2019
Volltextzugriff (PDF)
Details
- Autor(en) / Beteiligte
- Titel
- Chronic administration of LIMK2 inhibitors alleviates cavernosal veno-occlusive dysfunction through suppression of cavernosal fibrosis in a rat model of erectile dysfunction after cavernosal nerve injury
- Ist Teil von
- PloS one, 2019-03, Vol.14 (3), p.e0213586-e0213586
- Ort / Verlag
- United States: Public Library of Science
- Erscheinungsjahr
- 2019
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- We evaluated whether chronic administration of LIMK2-inhibitors could improve erectile function by alleviating CVOD through suppressing cavernosal fibrosis in a rat model of cavernosal nerve crush-injury (CNCI). Forty-two 12-week-old rats were equally categorized into the three groups: sham-surgery (S), CNCI (I), and CNCI treated with LIMK2-inhibitors (L). The L-group was treated with daily intraperitoneal injection of LIMK2-inhibitors (10.0 mg/kg) for 30-days after surgery. Erectile function was assessed using dynamic-infusion-cavernosometry (DIC). Penile tissue was processed for Masson's-trichrome staining, Western-blotting, and double immunofluorescence. The I-group showed significantly higher maintenance and drop rates as well as lower papaverine response, compared to the S-group. Chronic inhibition of LIMK2 in the L-group significantly improved the DIC parameters compared to those in the I-group, although the parameters were not completely restored to normal control values. Also, the I-group showed a reduced smooth muscle (SM)-to-collagen ratio, decreased immunohistochemical staining for α-SM-actin, increased number of fibroblasts positive for phosphorylated Cofilin, increased LIMK2/Cofilin phosphorylation and increased protein expression of Collagen-1 or Fibronectin, compared to the S-group. The L-group showed significant improvements in SM/collagen ratio and the deposition of Collagen-1 or Fibronectin compared to the I-group, although not completely normalized. According to the densitometry and confocal microscopy results, the L-group showed restoration of LIMK2/Cofilin phosphorylation and amount of fibroblasts positive for phosphorylated Cofilin to the normal control value. In conclusion, chronic inhibition of LIMK2 can improve CVOD and ED by alleviating cavernosal fibrosis via normalizing the LIMK2/Cofilin pathway.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 1932-6203eISSN: 1932-6203DOI: 10.1371/journal.pone.0213586Titel-ID: cdi_plos_journals_2191943467
- Format
- –
- Schlagworte
- Actin, Actin Depolymerizing Factors - metabolism, Actins - metabolism, Analysis, Animals, Apoptosis, Biology and Life Sciences, Care and treatment, Cofilin, Collagen, Confocal microscopy, Construction, Densitometers, Densitometry, Disease Models, Animal, Dosage and administration, Erectile dysfunction, Erectile Dysfunction - drug therapy, Erectile Dysfunction - enzymology, Erectile Dysfunction - pathology, Fibroblasts, Fibronectin, Fibronectins, Fibrosis, Fluorescent antibody technique, Hospitals, Immunofluorescence, Immunohistochemistry, Impotence, Inhibition, Inhibitors, Injuries, Kinase inhibitors, Lim Kinases - antagonists & inhibitors, Lim Kinases - metabolism, Male, Mathematical models, Medicine, Medicine and Health Sciences, Microscopy, Muscle proteins, Muscles, Normalizing, Parameters, Parasympathetic nervous system, Penis, Penis - enzymology, Penis - pathology, Peripheral Nerve Injuries - drug therapy, Peripheral Nerve Injuries - enzymology, Peripheral Nerve Injuries - pathology, Phosphorylation, Protein Kinase Inhibitors - pharmacology, Proteins, Rats, Research and Analysis Methods, Restoration, Rodents, Sexual disorders, Signal transduction, Signal Transduction - drug effects, Smooth muscle, Staining, Surgery, Treatment outcome, Urology