Increased expression of insulin-like growth factor-binding protein-3 is implicated in erectile dysfunction in two-kidney one-clip hypertensive rats after propranolol treatment

Zhou, Zhangyan; Yang, Zhonghua; Wang, Xinghuan; Hong, Changshou; Chen, Dong; Wang, Yongzhi; Zhou, Haihong; Peng, Mou; Liu, Quanliang; Wan, Shao-Ping

doi:10.1038/aja.2011.99

“…We have observed the higher expression of mRNA and protein of IGFBP-3 in old rat penile tissues which is related ED [3]. The higher expressions of IGFBP-3 were also observed in corpus cavernosum tissues of DM rats [13] and hypertensive rats [14]. It showed that IGFBP-3 might play an vital role in the development of ED.…”

Section: Changes Of Nos Activity and Of Cgmp Concentrationmentioning

confidence: 66%

Mesenchymal Stem Cells Modified with Short Hairpin RNA (shRNA) Constructs Targeting Insulin-like Growth Factor Binding Protein-3 (IGFBP-3) Improve Erectile Dysfunction in Old Rats

Pu

¹

,

Zhang

²

,

Zhou³

et al. 2020

Preprint

0

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Background: We have confirmed that injection of vector-based short hairpin RNA (shRNA) constructs targeting insulin-like growth factor binding protein-3 (IGFBP-3) in penis in old rat can improve erectile function. The aim of this study is to further determine the feasibility of bone marrowe derived mesenchymal stem cells (BM-MSCs) genetically modified with shRNA constructs targeting IGFBP-3 on improving erectile function in the aged rat. Methods: 40 old (24 months) male rats were randomized divided into 4 groups: PBS-only, BM-MSC treatment and LV3-shIGFBP-3 engineered BM-MSC treatment group (n=10/group).Ten 5-month-old rats were used as the young group. Four weeks after transplantation, the erectile function was assessed by cavernosal nerve stimulation. The percent of smooth muscle in corpus cavernosum was evaluated by masson’s trichrome staining. IGFBP-3 expression was estimated by Western blot. The cavernous insulin-like growth factor-1 (IGF-1) and vascular endothelial growth factor (VEGF) levels were analyzed after transplantation. Apoptosis in corpus cavernosum was measured using TUNEL and the activity of nitric oxide synthase (NOS) and concentration of guanosine 3’, 5’-cyclic-monophosphates (cGMP) in penile tissue were also analyzed. Results: Four weeks after intracavernous injection, BM-MSCs alone, especially LV3-shIGFBP-3 engineered BM-MSCs treatment rats had improvements in erectile function (p<0.05). The percentage of cavernosal smooth muscle was increased in BM-MSCs and LV3-shIGFBP-3 engineered BM-MSCs treatment group. IGFBP-3 protein expression was decreased obviously after injection of LV3-shIGFBP-3 engineered BM-MSCs. In addition, significant lower IGFBP-3 expression was associated with increased IGF-1 expression in LV3-shIGFBP-3 engineered BM-MSCs treatment rats although higher IGF-1 and VEGF concentrations were all determined after transplantation with BM-MSCs alone or BM-MSCs modified with LV3-shIGFBP-3. Lower levels of the apoptosis were also observed in the BM-MSCs and LV3-shIGFBP-3 engineered BM-MSCs treatment group. NOS activities and cGMP concentrations were also significantly increased after transplantation. Conclusions: These findings demonstrate that BM-MSCs alone or genetically modified with LV3-shIGFBP-3 can improve diminished erectile responses in the aged rat partially by increasing the smooth muscle integrity, increasing secretion of IGF-1 and VEGF, inhibiting apoptosis and increasing the NOS activity and cGMP accumulation.

show abstract

“…We have observed the higher expression of mRNA and protein of IGFBP-3 in old rat penile tissues which is related ED [3]. The higher expressions of IGFBP-3 were also observed in corpus cavernosum tissues of DM rats [13] and hypertensive rats [14]. It showed that IGFBP-3 might play an vital role in the development of ED.…”

Section: Discussionmentioning

confidence: 99%

Mesenchymal Stem Cells Modified With Short Hairpin RNA (shRNA) Constructs Targeting Insulin-like Growth Factor Binding Protein-3 (IGFBP-3) Improve Erectile Dysfunction in old Rats

Pu¹,

Zhang²,

Zhou³

et al. 2020

Preprint

0

View full text Add to dashboard Cite

Background: We have confirmed that injection of vector-based short hairpin RNA (shRNA) constructs targeting insulin-like growth factor binding protein-3 (IGFBP-3) in penis in old rat can improve erectile function. The aim of this study is to further determine the feasibility of bone marrowe derived mesenchymal stem cells (BM-MSCs) genetically modified with shRNA constructs targeting IGFBP-3 on improving erectile function in the aged rat. Methods: 40 old (24 months) male rats were randomized divided into 4 groups: PBS-only, BM-MSC treatment and LV3-shIGFBP-3 engineered BM-MSC treatment group (n=10/group).Ten 5-month-old rats were used as the young group. Four weeks after transplantation, the erectile function was assessed by cavernosal nerve stimulation. The percent of smooth muscle in corpus cavernosum was evaluated by masson’s trichrome staining. IGFBP-3 expression was estimated by Western blot. The cavernous insulin-like growth factor-1 (IGF-1) and vascular endothelial growth factor (VEGF) levels were analyzed after transplantation. Apoptosis in corpus cavernosum was measured using TUNEL and the activity of nitric oxide synthase (NOS) and concentration of guanosine 3’, 5’-cyclic-monophosphates (cGMP) in penile tissue were also analyzed. Results: Four weeks after intracavernous injection, BM-MSCs alone, especially LV3-shIGFBP-3 engineered BM-MSCs treatment rats had improvements in erectile function (p<0.05). The percentage of cavernosal smooth muscle was increased in BM-MSCs and LV3-shIGFBP-3 engineered BM-MSCs treatment group. IGFBP-3 protein expression was decreased obviously after injection of LV3-shIGFBP-3 engineered BM-MSCs. In addition, significant lower IGFBP-3 expression was associated with increased IGF-1 expression in LV3-shIGFBP-3 engineered BM-MSCs treatment rats although higher IGF-1 and VEGF concentrations were all determined after transplantation with BM-MSCs alone or BM-MSCs modified with LV3-shIGFBP-3. Lower levels of the apoptosis were also observed in the BM-MSCs and LV3-shIGFBP-3 engineered BM-MSCs treatment group. NOS activities and cGMP concentrations were also significantly increased after transplantation. Conclusions: These findings demonstrate that BM-MSCs alone or genetically modified with LV3-shIGFBP-3 can improve diminished erectile responses in the aged rat partially by increasing the smooth muscle integrity, increasing secretion of IGF-1 and VEGF, inhibiting apoptosis and increasing the NOS activity and cGMP accumulation.

show abstract

“…Erectile function was evaluated by measuring intracavernous pressure (ICP) following electrostimulation of the cavernous nerves at 4 weeks of propranolol treatment as previously described (Zhou et al ., ). Then, all rats were sacrificed with an i.p.…”

Section: Methodsmentioning

confidence: 97%

“…Although a previous report suggested that the decreased IGF‐1 availability could be associated with the development of ED in two‐kidney one‐clip (2K‐1C) hypertensive rats (Zhou et al ., ), there are no many studies on elucidating a relation between the decrease of the IGF‐1 availability and spontaneously hypertensive ED. So here we employed spontaneously hypertensive rats as a model to investigate the role of IGF‐1 on hypertensive ED in this study.…”

Section: Introductionmentioning

confidence: 99%

Decrease of the insulin-like growth factor-1 bioavailability in spontaneously hypertensive rats with erectile dysfunction

Zhou

¹

,

Cheng

²

,

Huang

³

et al. 2016

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We investigated the role of insulin-like growth factor-1 (IGF-1) in spontaneously hypertensive rats with erectile dysfunction. Firstly, we evaluated intracavernous pressure. The bioavailability of IGF-1 at both mRNA and protein levels were measured by quantitative real-time PCR and Western blot respectively. Then, cavernous cyclic guanosine monophosphate concentrations were detected by enzyme-linked immunosorbent assay. The cavernosal pressure was significantly decreased in the hypertensive and the propranolol treatment groups compared to the normal control group (P < 0.01). Cavernous IGF-1 bioavailability and the concentrations of cavernous cyclic guanosine monophosphate were both significantly decreased in the hypertensive and the propranolol treatment groups compared to the normal control group (P < 0.01). This study suggests that an obvious decrease in cavernous IGF-1 levels might play an important role in spontaneously hypertensive rats with erectile dysfunction.

show abstract

Increased expression of insulin-like growth factor-binding protein-3 is implicated in erectile dysfunction in two-kidney one-clip hypertensive rats after propranolol treatment

Cited by 9 publications

References 19 publications

Mesenchymal Stem Cells Modified with Short Hairpin RNA (shRNA) Constructs Targeting Insulin-like Growth Factor Binding Protein-3 (IGFBP-3) Improve Erectile Dysfunction in Old Rats

Mesenchymal Stem Cells Modified with Short Hairpin RNA (shRNA) Constructs Targeting Insulin-like Growth Factor Binding Protein-3 (IGFBP-3) Improve Erectile Dysfunction in Old Rats

Mesenchymal Stem Cells Modified With Short Hairpin RNA (shRNA) Constructs Targeting Insulin-like Growth Factor Binding Protein-3 (IGFBP-3) Improve Erectile Dysfunction in old Rats

Decrease of the insulin-like growth factor-1 bioavailability in spontaneously hypertensive rats with erectile dysfunction

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