Nitric Oxide Prevents Mouse Embryonic Stem Cell Differentiation Through Regulation of Gene Expression, Cell Signaling, and Control of Cell Proliferation

Tapia-Limonchi, Rafael; Cahuana, Gladys M.; Caballano-Infantes, Estefanía; Salguero-Aranda, Carmen; Beltrán-Povea, Amparo; Hitos, Ana B.; Hmadcha, Abdelkrim; Martı́n, Franz; Soria, Bernat; Bedoya, Francisco J.; Tejedo, Juan R.

doi:10.1002/jcb.25513

Cited by 17 publications

(16 citation statements)

References 27 publications

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“…In our study, more NO was released from ADSCs-iNOS than ADSCs. Tapia-Limonchi et al found that NO maintained embryonic stem cells (ESC) pluripotency and delayed ESC differentiation by regulating Gsk3-β/β-catenin and PI3K/Akt signaling pathways (Tapia-Limonchi et al, 2016). The effect of NO released from ADSCs iNOS on ADSC stemness required further investigation.…”

Section: Discussionmentioning

confidence: 99%

Peer Review #1 of "Transplantation of adipose-derived stem cells overexpressing inducible nitric oxide synthase ameliorates diabetes mellitus-induced erectile dysfunction in rats (v0.1)"

2019

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Background: Erectile dysfunction is a major complication of diabetes mellitus. Adipose derived stem cells (ADSCs) have attracted much attention as a promising tool for the treatment of diabetes mellitus induced erectile dysfunction (DMED). Inducible nitric oxide synthase (iNOS) plays an important role in protecting penile tissues from fibrosis. The aim of this study was to determine the efficacy of ADSCs overexpressing iNOS on DMED in rats. Methods: ADSCs were isolated and infected with adenovirus overexpressing iNOS (named as ADSCs-iNOS). The expression of iNOS was detected using western blot analysis and real-time PCR. Rats were randomly assigned into five groups: control group, DMED group, ADSCs group, ADSCs-EGFP group and ADSCs-iNOS group. 5×10 5 cells were given once via the intracorporal route. Two weeks after treatment, erectile function was assessed by electrical stimulation of the cavernous nerve. Penile tissues were obtained and evaluated at histology level. Results: We found that ADSCs-iNOS had significantly higher expression of iNOS at mRNA and protein levels and generated more nitric oxide. ADSCs-iNOS reduced collagen I and collagen IV expression of corpus cavernosum smooth muscle cells (CCSMCs) in cell co-culture model. Transforming growth factor-β1 expression in CCSMCs reduced following co-culture with ADSCs-iNOS. Injection of ADSCs-iNOS significantly ameliorated DMED in rats and decreased collagen/smooth muscle cell ratio of penile tissues. Moreover, elevated nitric oxide and cGMP concentrations were detected in penile tissues of ADSCs-iNOS group. Conclusion: Taken together, ADSCs-iNOS significantly improved erectile function of DMED rats. The therapeutic effect may be achieved by increased nitric oxide generation and the suppression of collagen I and collagen IV expression in the CCSMCs to decrease penile fibrosis.

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Section: Discussionmentioning

confidence: 99%

Peer Review #1 of "Transplantation of adipose-derived stem cells overexpressing inducible nitric oxide synthase ameliorates diabetes mellitus-induced erectile dysfunction in rats (v0.1)"

2019

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show abstract

“…In our study, more NO were released from ADSCs-iNOS than ADSCs. Tapia-Limonchi et al found that NO maintained embryonic stem cells (ESC) pluripotency and delayed ESC differentiation by regulating Gsk3-β/β-catenin and PI3K/Akt signaling pathways (Tapia-Limonchi et al, 2016). The effect of NO released from ADSCs iNOS on ADSC stemness required further investigation.…”

Section: Discussionmentioning

confidence: 99%

Transplantation of adipose derived stem cells overexpressing inducible nitric oxide synthase ameliorates diabetes mellitus induced erectile dysfunction in rats

Zhang

Yang

Zhuan

et al. 2019

Preprint

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Background: Erectile dysfunction is a major complication of diabetes mellitus. Adipose derived stem cells (ADSCs) has attracted much attention as a promising tool for the treatment of diabetes mellitus induced erectile dysfunction (DMED). Inducible nitric oxide synthase (iNOS) plays an important role in protecting penile tissues from fibrosis. The aim of this study was to determine the efficacy of ADSCs overexpressing iNOS on DMED in rats. Methods: ADSCs were isolated and infected with adenovirus overexpressing iNOS (named as ADSCs-iNOS). The expression of iNOS was detected using western blot analysis and real-time PCR. Rats were randomly assigned into five groups: control group, DMED group, ADSCs group, ADSCs-EGFP group and ADSCs-iNOS group. 5×105 cells were given once via the intracorporal route. Two weeks after treatment, erectile function was assessed by electrical stimulation of the cavernous nerve. Penile tissues were obtained and evaluated at histology level. Results: We found that ADSCs-iNOS had significantly higher expression of iNOS at mRNA and protein levels and generated more nitric oxide. ADSCs-iNOS reduced collagen I and collagen IV expression of corpus cavernosum smooth muscle cells (CCSMCs) in cell co-culture model. Transforming growth factor-β1 expression and p-Smad2/3 to Smad2/3 ratio in CCSMCs reduced following co-culture with ADSCs-iNOS. Injection of ADSCs-iNOS significantly ameliorated DMED in rats and decreased collagen/smooth muscle cell ratio of penile tissues. Moreover, elevated nitric oxide and cGMP concentrations were detected in penile tissues of ADSCs-iNOS group. Conclusion: Taken together, ADSCs-iNOS significantly improve erectile function of DMED rats. The therapeutic effect may be achieved by increased nitric oxide generation and the suppression of collagen I and collagen IV expression in the CCSMCs to decrease penile fibrosis.

show abstract

“…In our study, more NO was released from ADSCs-iNOS than ADSCs. Tapia-Limonchi et al (2016) found that NO maintained embryonic stem cells (ESC) pluripotency and delayed ESC differentiation by regulating Gsk3-β/β-catenin and PI3K/Akt signaling pathways. The effect of NO released from ADSCs iNOS on ADSC stemness required further investigation.…”

Section: Discussionmentioning

confidence: 99%

Transplantation of adipose-derived stem cells overexpressing inducible nitric oxide synthase ameliorates diabetes mellitus-induced erectile dysfunction in rats

Zhang

Yang

et al. 2019

PeerJ

View full text Add to dashboard Cite

Background Erectile dysfunction is a major complication of diabetes mellitus. Adipose-derived stem cells (ADSCs) have attracted much attention as a promising tool for the treatment of diabetes mellitus-induced erectile dysfunction (DMED). Inducible nitric oxide synthase (iNOS) plays an important role in protecting penile tissues from fibrosis. The aim of this study was to determine the efficacy of ADSCs overexpressing iNOS on DMED in rats. Methods ADSCs were isolated and infected with adenovirus overexpressing iNOS (named as ADSCs-iNOS). The expression of iNOS was detected using western blot analysis and real-time PCR. Rats were randomly assigned into five groups: control group, DMED group, ADSCs group, ADSCs-EGFP group and ADSCs-iNOS group. 5 × 105 cells were given once via the intracorporal route. Two weeks after treatment, erectile function was assessed by electrical stimulation of the cavernous nerve. Penile tissues were obtained and evaluated at histology level. Results We found that ADSCs-iNOS had significantly higher expression of iNOS at mRNA and protein levels and generated more nitric oxide (NO). ADSCs-iNOS reduced collagen I and collagen IV expression of corpus cavernosum smooth muscle cells (CCSMCs) in cell co-culture model. Transforming growth factor-β1 expression in CCSMCs reduced following co-culture with ADSCs-iNOS. Injection of ADSCs-iNOS significantly ameliorated DMED in rats and decreased collagen/smooth muscle cell ratio of penile tissues. Moreover, elevated NO and cyclic guanosine monophosphate concentrations were detected in penile tissues of ADSCs-iNOS group. Conclusion Taken together, ADSCs-iNOS significantly improved erectile function of DMED rats. The therapeutic effect may be achieved by increased NO generation and the suppression of collagen I and collagen IV expression in the CCSMCs to decrease penile fibrosis.

show abstract

Nitric Oxide Prevents Mouse Embryonic Stem Cell Differentiation Through Regulation of Gene Expression, Cell Signaling, and Control of Cell Proliferation

Cited by 17 publications

References 27 publications

Peer Review #1 of "Transplantation of adipose-derived stem cells overexpressing inducible nitric oxide synthase ameliorates diabetes mellitus-induced erectile dysfunction in rats (v0.1)"

Peer Review #1 of "Transplantation of adipose-derived stem cells overexpressing inducible nitric oxide synthase ameliorates diabetes mellitus-induced erectile dysfunction in rats (v0.1)"

Transplantation of adipose derived stem cells overexpressing inducible nitric oxide synthase ameliorates diabetes mellitus induced erectile dysfunction in rats

Transplantation of adipose-derived stem cells overexpressing inducible nitric oxide synthase ameliorates diabetes mellitus-induced erectile dysfunction in rats

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