Suppression of Cavernosal Fibrosis in a Rat Model

Cho, Min Chul; Song, Won Hoon; Paick, Jae Seung

doi:10.1016/j.sxmr.2018.02.007

Cited by 33 publications

(21 citation statements)

References 60 publications

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“…Cavernosal fibrosis is an important pathological process leading to ED [20] and can be determined by Masson's trichrome staining. Compared to the NC group, the M group exhibited a clear decrease in corporal smooth muscle content and an increase in collagen deposition ( P < 0.0001) (Figure 3(a)).…”

Section: Resultsmentioning

confidence: 99%

“…At present, the relationship between RhoA/ROCK signaling and ED has attracted the attention of many researchers. RhoA/ROCK pathway activation is closely related to erectile function, as well as cavernosal and penile fibrosis [20, 26]. The inhibition of ROCK1 or its downstream molecules, LIMK2 and Coflin, has been shown to effectively attenuate penile fibrosis.…”

Section: Discussionmentioning

confidence: 99%

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Effect of HongJing I in Treating Erectile Function and Regulating RhoA Pathway in a Rat Model of Bilateral Cavernous Nerve Injury

Zhao

et al. 2019

Evidence-Based Complementary and Alternative Medicine

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HongJing I (HJI), a traditional Chinese herbal formula, has been confirmed to be effective for the clinical treatment of erectile dysfunction (ED). However, the mechanism of action of HJI remains unclear. Here, we aimed to investigate the effect and underlying mechanisms of HJI against ED in a rat model of bilateral cavernous nerve injury (BCNI). Rats were divided into five groups: normal control (NC), BCNI-induced ED model (M), M + low-dose HJI (HL), M + medium-dose HJI (HM), and M + high-dose HJI (HH). All groups were treated with normal saline or the relevant drug for 28 consecutive days after inducing BCNI-ED. At the end of the treatment period, the intracavernous pressure (ICP) was recorded, and histological examination was conducted using Masson’s trichrome staining. Immunofluorescence staining and western blotting were applied to detect the changes in fibrosis protein and Ras homolog A (RhoA), Rho-associated protein kinase 1 (ROCK1), and ROCK2 expression. We found that HJI effectively improved the ICP in the treatment groups. In addition, RhoA, ROCK1, and ROCK2 expression levels were increased upon BCNI-ED induction, and HJI successfully inhibited cavernosum fibrosis and the activation of RhoA/ROCK2 signaling. Overall, these results suggest that the effects of HJI in attenuating ED may be caused, at least in part, by the suppression of RhoA/ROCK2 signaling and alleviation of fibrosis. However, the precise mechanism surrounding this requires further investigation in future studies.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Effect of HongJing I in Treating Erectile Function and Regulating RhoA Pathway in a Rat Model of Bilateral Cavernous Nerve Injury

Zhao

et al. 2019

Evidence-Based Complementary and Alternative Medicine

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“…Wang et al showed that castration of adult male Sprague-Dawley rats resulted in greater fibrosis, decreased smooth muscle/collagen ratio, and higher expression of TGF-b1, all of which were partly restored with T administration. 12 A review of cavernosal fibrosis 13 The authors proposed that strategies to minimize the impact of TGF-b1-signaling pathways might, therefore, be beneficial for attenuating fibrotic conditions of the penis, such as PD. The gene for TGF-b1 has been found to be overexpressed in PD.…”

Section: Discussionmentioning

confidence: 99%

Augmenting Intralesional Collagenase Treatment with Testosterone Therapy Provides Greater Self-Assessed Improvement in Penile Curvature due to Peyronie's Disease

Shlykova

Morgentaler

2020

Androgens: Clinical Research and Therapeutics

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Introduction: Testosterone (T) deficiency has been reported to be associated with Peyronie's disease (PD). This study investigated response rates to intralesional injections of collagenase clostridium histolyticum (XiaflexÔ) (CCx) for penile curvature in men who simultaneously received T therapy (TTh) and in men who received CCx without TTh. Methods: Search of electronic records identified all men treated with CCx from 2013 to 2018, and whether they also received TTh during that time. Laboratory results for baseline serum T, free T, and luteinizing hormone were available for all men. Response to CCx was categorized as no change, mild change, substantial change, or complete resolution based on subjective reports by patients. Results: A total of 117 men received treatment with CCx. Of these, 72 received CCx alone (henceforth referred to as XA group) and 45 received CCx plus TTh (referred to as XT group). Mean baseline serum T was 458 ng/dL for the XA group and 384 ng/dL for the XT group (p = 0.10). Mean age was 60.4 years for the XT group and 56.5 years for the XA group (p = 0.028). Baseline mean curvature was 46°for the XA group and 45°for the XT group. Mean number of treatment cycles (two injections per cycle) was 2.7 for both groups. Overall, 67.5% reported some improvement in curve with CCx. Reports of any improvement were 84.4% for the XT group and 56.9% for the XA group (p < 0.001). Conversely, rates of no improvement were 15.6% for the XT group and 43.1% for the XA group. Substantial improvement or complete resolution of curve was noted by 48.8% of the XT group and 20.8% of the XA group (p = 0.001). Conclusions: These pilot observational results suggest that TTh may improve the response to intralesional CCx treatment of PD. A prospective study is warranted to investigate this further.

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“…Histological analysis of CC has been mainly performed on pathological conditions including diabetes and aged samples 17 . It has been suggested that accumulation of fibrosis is reported in such conditions 18 . Augmented expression of collagen and other ECM components have been reported in case of fibrosis of pathogenic CC 19 .…”

Section: Introductionmentioning

confidence: 99%

3D reconstruction and histopathological analyses on murine corporal body

Hashimoto

Kajimoto

Ueda

et al. 2021

Reprod Medicine & Biology

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Purpose Erectile dysfunction (ED) is one of the increasing diseases with aging society. The basis of ED derived from local penile abnormality is poorly understood because of the complex three‐dimensional (3D) distribution of sinusoids in corpus cavernosum (CC). Understanding the 3D histological structure of penis is thus necessary. Analyses on the status of regulatory signals for such abnormality are also performed. Methods To analyze the 3D structure of sinusoid, 3D reconstruction from serial sections of murine CC were performed. Histological analyses between young (2 months old) and aged (14 months old) CC were performed. As for chondrogenic signaling status of aged CC, SOX9 and RBPJK staining was examined. Results Sinusoids prominently developed in the outer regions of CC adjacent to tunica albuginea. Aged CC samples contained ectopic chondrocytes in such regions. Associating with the appearance of chondrocytes, the expression of SOX9, chondrogenic regulator, was upregulated. The expression of RBPJK, one of the Notch signal regulators, was downregulated in the aged CC. Conclusions Prominent sinusoids distribute in the outer region of CC which may possess important roles for erection. A possibility of ectopic chondrogenesis induced by alteration of SOX9/Notch signaling with aging is indicated.

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Suppression of Cavernosal Fibrosis in a Rat Model

Cited by 33 publications

References 60 publications

Effect of HongJing I in Treating Erectile Function and Regulating RhoA Pathway in a Rat Model of Bilateral Cavernous Nerve Injury

Effect of HongJing I in Treating Erectile Function and Regulating RhoA Pathway in a Rat Model of Bilateral Cavernous Nerve Injury

Augmenting Intralesional Collagenase Treatment with Testosterone Therapy Provides Greater Self-Assessed Improvement in Penile Curvature due to Peyronie's Disease

3D reconstruction and histopathological analyses on murine corporal body

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