IcarisideII facilitates the differentiation of ADSCs to SCs via let-7i/STAT3 axis to preserve erectile function

Abstract Background IcarisideII (ICAII) could promote the differentiation of adipose tissue-derived stem cells (ADSCs) to Schwann cells (SCs), leading to improvement of erectile function (EF) and providing a realistic therapeutic option for the treatment of erectile dysfunction (ED). However, the un...

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Main Authors: Pingyu Ge, Yinxue Guo, Jun Shen
Format: Article
Language:English
Published: BMC 2019-10-01
Series:Biological Research
Subjects:
Online Access:http://link.springer.com/article/10.1186/s40659-019-0262-3
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author Pingyu Ge
Yinxue Guo
Jun Shen
author_facet Pingyu Ge
Yinxue Guo
Jun Shen
author_sort Pingyu Ge
collection DOAJ
description Abstract Background IcarisideII (ICAII) could promote the differentiation of adipose tissue-derived stem cells (ADSCs) to Schwann cells (SCs), leading to improvement of erectile function (EF) and providing a realistic therapeutic option for the treatment of erectile dysfunction (ED). However, the underlying molecular mechanisms of ADSCs and ICAII in this process remain largely unclear. Methods ADSCs were treated with different concentrations of ICAII. Cell proliferation was determined by MTT assay. qRT-PCR and western blot were performed to detect expressions of SCs markers, signal transducer and activator of transcription-3 (STAT3), and microRNA-let-7i (let-7i). Luciferase reporter assay was conducted to verify the regulatory relationship between let-7i and STAT3. The detection of intracavernosal pressure (ICP) and the ratio of ICP/mean arterial pressure (MAP) were used to evaluate the EF in bilateral cavernous nerve injury (BCNI) rat models. Results ICAII promoted cell proliferation of ADSCs in a dose-dependent manner. The mRNA and protein levels of SCs markers were increased by ICAII treatment in a dose-dependent manner in ADSCs. Moreover, let-7i was significantly decreased in ICAII-treated ADSCs and upregulation of let-7i attenuated ICAII-induced promotion of SCs markers. In addition, STAT3 was a direct target of let-7i and upregulated in ICAII-treated ADSCs. Interestingly, overexpression of STAT3 abated the let-7i-mediated inhibition effect on differentiation of ADSCs to SCs and rescued the ICAII-mediated promotion effect on it. Besides, combination treatment of ADSCs and ICAII preserved the EF of BCNI rat models, which was undermined by let-7i overexpression. Conclusion ICAII was effective for preserving EF by promoting the differentiation of ADSCs to SCs via modulating let-7i/STAT3 pathway.
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spelling doaj.art-12f47d71f7ef4c04b1d24be511453d852022-12-21T18:21:19ZengBMCBiological Research0717-62872019-10-015211810.1186/s40659-019-0262-3IcarisideII facilitates the differentiation of ADSCs to SCs via let-7i/STAT3 axis to preserve erectile functionPingyu Ge0Yinxue Guo1Jun Shen2Department of Urology Surgery, the First Affiliated Hospital of Guizhou University of Traditional Chinese MedicineDepartment of Nephrology, the First Affiliated Hospital of Guizhou University of Traditional Chinese MedicineDepartment of Urology Surgery, the First Affiliated Hospital of Guizhou University of Traditional Chinese MedicineAbstract Background IcarisideII (ICAII) could promote the differentiation of adipose tissue-derived stem cells (ADSCs) to Schwann cells (SCs), leading to improvement of erectile function (EF) and providing a realistic therapeutic option for the treatment of erectile dysfunction (ED). However, the underlying molecular mechanisms of ADSCs and ICAII in this process remain largely unclear. Methods ADSCs were treated with different concentrations of ICAII. Cell proliferation was determined by MTT assay. qRT-PCR and western blot were performed to detect expressions of SCs markers, signal transducer and activator of transcription-3 (STAT3), and microRNA-let-7i (let-7i). Luciferase reporter assay was conducted to verify the regulatory relationship between let-7i and STAT3. The detection of intracavernosal pressure (ICP) and the ratio of ICP/mean arterial pressure (MAP) were used to evaluate the EF in bilateral cavernous nerve injury (BCNI) rat models. Results ICAII promoted cell proliferation of ADSCs in a dose-dependent manner. The mRNA and protein levels of SCs markers were increased by ICAII treatment in a dose-dependent manner in ADSCs. Moreover, let-7i was significantly decreased in ICAII-treated ADSCs and upregulation of let-7i attenuated ICAII-induced promotion of SCs markers. In addition, STAT3 was a direct target of let-7i and upregulated in ICAII-treated ADSCs. Interestingly, overexpression of STAT3 abated the let-7i-mediated inhibition effect on differentiation of ADSCs to SCs and rescued the ICAII-mediated promotion effect on it. Besides, combination treatment of ADSCs and ICAII preserved the EF of BCNI rat models, which was undermined by let-7i overexpression. Conclusion ICAII was effective for preserving EF by promoting the differentiation of ADSCs to SCs via modulating let-7i/STAT3 pathway.http://link.springer.com/article/10.1186/s40659-019-0262-3Erectile functionADSCslet-7iSTAT3ICAII
spellingShingle Pingyu Ge
Yinxue Guo
Jun Shen
IcarisideII facilitates the differentiation of ADSCs to SCs via let-7i/STAT3 axis to preserve erectile function
Biological Research
Erectile function
ADSCs
let-7i
STAT3
ICAII
title IcarisideII facilitates the differentiation of ADSCs to SCs via let-7i/STAT3 axis to preserve erectile function
title_full IcarisideII facilitates the differentiation of ADSCs to SCs via let-7i/STAT3 axis to preserve erectile function
title_fullStr IcarisideII facilitates the differentiation of ADSCs to SCs via let-7i/STAT3 axis to preserve erectile function
title_full_unstemmed IcarisideII facilitates the differentiation of ADSCs to SCs via let-7i/STAT3 axis to preserve erectile function
title_short IcarisideII facilitates the differentiation of ADSCs to SCs via let-7i/STAT3 axis to preserve erectile function
title_sort icarisideii facilitates the differentiation of adscs to scs via let 7i stat3 axis to preserve erectile function
topic Erectile function
ADSCs
let-7i
STAT3
ICAII
url http://link.springer.com/article/10.1186/s40659-019-0262-3
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AT yinxueguo icarisideiifacilitatesthedifferentiationofadscstoscsvialet7istat3axistopreserveerectilefunction
AT junshen icarisideiifacilitatesthedifferentiationofadscstoscsvialet7istat3axistopreserveerectilefunction