间充质干细胞蛋白多糖Agrin促进尿失禁功能恢复的机制研究

项目来源

国家自然科学基金(NSFC)

项目主持人

江海红

项目受资助机构

温州医科大学

立项年度

2016

立项时间

未公开

项目编号

81670695

项目级别

国家级

研究期限

未知 / 未知

受资助金额

51.00万元

学科

医学科学-泌尿系统-泌尿系统疾病研究新技术与新方法

学科代码

H-H05-H0511

基金类别

面上项目

关键词

蛋白多糖 ; 干细胞 ; 产伤 ; 生物标志物 ; 尿失禁 ; urinary incontinence ; stem cell ; proteoglycan ; biomarker ; birth injury

参与者

王思齐;林峰;李海燕;陈洪德;黄航;李仕;叶翔翔;林琦;蒋海波

参与机构

温州医科大学

项目标书摘要:利用间充质干细胞(mesenchymal stem cells,MSCs)受趋化因子归巢到损伤部位是干细胞治疗研究的重要策略之一,我们发现CCL7因子在产伤后压力性尿失禁(stress urinary incontinence,SUI)动物尿道局部大量表达,并对MSCs在尿道局部聚集活化显著。据此通过SILAC等蛋白筛查发现并确认CCL7刺激后MSCs的Agrin及下游通路蛋白显著升高;进一步临床上对手术治疗SUI病人筛查CCL7及Agrin,发现Agrin表达显著减少和曾有严重产伤后SUI显著相关。CCL7可能通过Agrin使MSCs活化并促进产伤后SUI恢复。本研究拟在此基础上进行相应的临床、细胞、分子、及动物实验,论证CCL7/Agrin表达缺陷预示产妇发生产伤后SUI危险增加,解析CCL7通过Agrin调控下游通路的分子机制;为进一步深入研究MSCs防治产伤后及后期SUI提供基础。

Application Abstract: Use of mesenchymal stem cells(MSCs)homing to damaged tissue by local specific chemokine is one of the important strategies for stem cell treatment research.We found cytokine CCL7 expression increase in significance in urethra on stress urinary incontinence(SUI)animal model of childbirth injury,which can increase local gathering and activating MSCs to urethra significantly.Then we used SILAC screening and related testing found and confirmed MSCs agrin and its downstream pathway proteins increases in significance after CCL7 stimulation.Furthermore,in clinic,we found there was a significant correlation for SUI patients whose Agrin responsive expression defect during the anti-SUI sling procedure with SUI patients who have had serious SUI after childbirth injury.Therefore,Agrin might help SUI recovery through the mechanism of CCL7 interacting with Agrin to gather and activate MSCs at local injured urethra.In this study,utilizing clinical trial and related mocular and SUI animal model experiments;we will confirm if the defects on CCL7 or Agrin reactive expression after maternal injury to urethra will increase the risk SUI after childbirth injury.We will also clarify the detail mechanism of CCL7 interact with Agrin and its downstream pathway regulation.This investigation will provide an important basis for understanding and further in-depth study of the MSCs for alleviating maternal SUI and later SUI incidence and prevalence.

项目受资助省

浙江省

项目结题报告(全文)

间充质干细胞(mesenchymal stem cells,MSCs)受趋化因子趋化聚集到损伤部位是干细胞治疗研究的重要策略之一,通过本课题研究,我们确认了CCL7因子在产伤后压力性尿失禁(stress urinary incontinence,SUI)动物模型的尿道局部表达显著升高,CCL7干预能够显著增强MSCs在尿道局部的聚集和活化;我们阐明了CCL7主要是通过Agrin来促进局部MSCs的聚集和活化,并可以促进产伤后SUI的控尿功能恢复;论证了其主要是通过CCL7-MSCs-Agrin通路,并影响下游Agrin-Lrp4-MuSK轴信号分子机制来活化。进一步的延伸研究中,我们还发现了MSCs聚集活化后对尿道局部微环境的局部成纤维细胞代谢有显著影响,这将为我们继续深入研究打下基础依据,也为进一步临床开发应用MSCs及其分泌物为基础的细胞学治疗尿失禁提供基础理论依据。

  • 排序方式:
  • 2
  • /
  • 1.Questionnaire Survey on the Current Situation and Experience in Prevention and Control Measures at Urology Clinics During the COVID-19 Epidemic in China

    • 关键词:
    • COVID-19; experience; SARS-CoV-2; questionnaire; urological outpatient;epidemic;ACUTE KIDNEY INJURY; OUTCOMES
    • Zhu, Xiao-Liang;Jiang, Hai-Hong;Jiang, Ming-Hui;Liu, Wen-Li;Sheng, Zi-Lu;Liu, Jia-Hui;Wang, Meihao
    • 《FRONTIERS IN PUBLIC HEALTH》
    • 2021年
    • 9卷
    • 期刊

    COVID-19, the coronavirus disease 2019; SARS-CoV-2, the coronavirus 2; ACE2, angiotensin converting enzyme 2; S protein, spiked glycoprotein; TMPRSS2, transmembrane serine protease 2; WHO, World Health Organization. Purpose: Although the coronavirus disease 2019 (COVID-19) pandemic, caused by the severe acute respiratory syndrome coronavirus 2, has been viably controlled in China, a new normal in healthcare strategies has become standard in China and worldwide. We conducted a questionnaire study to disseminate the experience from China in terms of urology outpatient prevention and control measures under standardized prevention policies against COVID-19. Participants and Methods: From May 3, 2020 to June 25, 2020, we conducted an anonymous cross-sectional questionnaire study, focused on the status of and experiences with outpatient urology prevention and control measures during the COVID-19 pandemic. The targeted respondents were urologists in mainland China, covering all levels of hospitals and clinics. Results: A total of 216 (97%) valid responses were collected. We found that 183 (85%) respondents were from outside of Hubei province in China. One-hundred-and-fifty-eight (73%) respondents believed that SARS-CoV-2 could be detected in urine, and that protection against urine exposure was needed. Over 80% of respondents recommended WeChat application or similar online video meetings for virtual outpatient consultations. The suggested flowcharts and recommendations to prevent new cases were easy to understand and approved by most physicians, which could provide reference for outpatient prevention and control. We still need to make adequate preparations under the new normal of the COVID-19 Epidemic, especially for those suspected of being infected. Conclusions: Although the scientific validation of the questionnaire is limited, it provides a first snapshot of the experiences relating to the prevention and control measures in urology clinics in China, and can inform future policies in this field.

    ...
  • 2.Bone marrow stem cells secretome accelerates simulated birth trauma-induced stress urinary incontinence recovery in rats

    • 《AGING-US》
    • 2021年
    • 13卷
    • 7期
    • 期刊

    Stress urinary incontinence (SUI) is defined as involuntary urine leakage during physical activities that increase the intra-abdominal pressure on the bladder. We studied bone marrow stem cell (BMSC) secretome-induced activation of anterior vaginal wall (AVW) fibroblasts and its ability to accelerate SUI recovery following vaginal distention (VD) in a rat model of birth trauma using BMSC-conditioned medium (BMSC-CM) and concentrated conditioned medium (CCM). BMSC-CM enhanced the proliferation, migration, and collagen synthesizing abilities of fibroblasts. Differentially expressed genes in BMSC-CM-induced fibroblasts were mainly enriched for cell adhesion, extracellular fibril organization and angiogenesis. Treatment with the JAK2 inhibitor AG490 reversed BMSC-CM-induced activation of the JAK2/STAT4 pathway. Periurethral injection with BMSC-CCM markedly enhanced the abdominal leak point pressure (LPP) in rats after VD. Histological analysis revealed increased numbers of fibroblasts, improved collagen fibers arrangement and elevated collagens content in the AVW of rats receiving BMSC-CCM. These findings suggest the BMSC secretome activates AVW fibroblasts and contributes to the functional and anatomic recovery of simulated birth trauma-induced SUI in rats.

    ...
  • 3.基于认知行为疗法的院外护理干预对单纯雄激素剥夺治疗的前列腺癌患者影响

    • 关键词:
    • 认知疗法;护理;前列腺癌;雄激素剥夺治疗
    • 冯瑶;李海燕;黄航;陈建霞;张海微;吴蓉蓉;江海红
    • 《中国现代医生》
    • 2021年
    • 20期
    • 期刊

    目的研究基于认知行为疗法(CBT)的院外护理干预对单纯雄激素剥夺治疗的老年前列腺癌患者跌倒风险的影响,为提高此类患者的护理质量提供临床依据。方法将2018年10月至2019年10月我院符合纳入标准的120例诊断为前列腺癌并行单纯雄激素剥

    ...
  • 4.Management of pelvic organ prolapse of ruptured and extruded bladder from a rare complication of vaginal hysterectomy: a case presentation

    • 《BMC SURGERY》
    • 2021年
    • 21卷
    • 1期
    • 期刊

    Background The prolapse of a ruptured and extruded bladder after vaginal hysterectomy is rare in clinical practice. We report the case of a significant mass that prolapsed from the vagina after a vaginal hysterectomy in a multiparous postmenopausal woman. Case presentation A 67-year old multiparous postmenopausal Chinese woman was found to have a significant mass extruding from the vagina after a vaginal hysterectomy. The mass was a ruptured and everted bladder, and the diagnosis was confirmed after physical and imaging examinations and urethral catheterization. The patient underwent an emergency operation for mass reduction, bladder repair, and partial colpocleisis under general anesthesia. She recovered without prolapse or urinary drainage complications after 35 months of follow-up. Conclusions The present case serves as a guide for the management of patients with pelvic organ prolapse. The condition of patients should be carefully evaluated before surgery, and individualized operation should be performed. Careful postoperative follow-up is crucial for the timely exclusion of complications, especially in elderly patients with persistently increased abdominal pressure.

    ...
  • 6.Combined Treatment With CCR1-Overexpressing Mesenchymal Stem Cells and CCL7 Enhances Engraftment and Promotes the Recovery of Simulated Birth Injury-Induced Stress Urinary Incontinence in Rats

    • 关键词:
    • stress urinary incontinence; mesenchymal stem cell; chemokine (c-cmotif) ligand 7; chemokine (c-c motif) receptor 1; rat model; birthinjury;CHILDBIRTH INJURIES; VAGINAL DISTENSION; PUDENDAL NERVE; HOMING FACTOR;MIGRATION; EXPRESSION; TRAFFICKING; CHEMOKINES; THERAPY; MUSCLE
    • Jiang, Hai-Hong;Ji, Ling-Xiao;Li, Hai-Yan;Song, Qi-Xiang;Bano, Yasmeen;Chen, Lei;Liu, Guiming;Wang, Meihao
    • 《FRONTIERS IN SURGERY》
    • 2020年
    • 7卷
    • 期刊

    Objective: To observe whether urethral injection of chemokine (c-c motif) ligand 7 (CCL7) and overexpressing CC receptor 1 (CCR1) in mesenchymal stem cells (MSCs) can promote their homing and engraftment to the injured tissue, and improve the recovery of simulated birth injury-induced stress urinary incontinence (SUI) in rats.Methods: Female rats underwent a dual injury consisting of vaginal distension (VD) and pudendal nerve crush (PNC) to induce SUI. Bone marrow-derived MSCs were transduced with lentivirus carrying CCR1 (MSC-CCR1) and green fluorescent protein (GFP). Forty virgin Sprague-Dawley rats were evenly distributed into four groups: sham SUI + MSC-CCR1+CCL7, SUI + MSCs, SUI + MSC-CCR1, and SUI + MSC-CCR1+CCL7 group. The engrafted MSCs in urethra were quantified. Another three groups of rats, including sham SUI + sham MSC-CCR1+CCL7 treatment, SUI + sham MSC-CCR1+CCL7 treatment, and SUI + MSC-CCR1+CCL7 treatment group, were used to evaluate the functional recovery by testing external urethral sphincter electromyography (EUS EMG), pudendal nerve motor branch potentials (PNMBP), and leak point pressure (LPP) 1 week after injury and injection. Urethra and vagina were harvested for histological examination.Results: The SUI + MSC-CCR1+CCL7 group received intravenous injection of CCR1-overexpressing MSCs and local injection of CCL7 after simulated birth injury had the most engraftment of MSCs to the injured tissues and best functional recovery from SUI compared to other groups. Histological examination showed a partial repair in the SUI + MSC-CCR1+CCL7 group.Conclusions: Our study demonstrated combined treatment with CCR1-overexpressing MSCs and CCL7 can increase engraftment of MSCs and promote the functional recovery of simulated birth trauma-induced SUI in rats, which could be a new therapeutic strategy for SUI.

    ...
  • 7.Case Report: Management of Multiple Deep-Tissue Cellulitis Without Sling Removal After an Anti-incontinence Procedure in a Female With Diabetes Mellitus

    • 关键词:
    • tension-free vaginal tape transobturator (TVT-O); stress urinaryincontinence (SUI); type 2 diabetes; cellulitis; synthetic sling;COMPLICATIONS; OUTCOMES
    • Jiang, Hai-Hong;Hu, Sheng-Ping;Bano, Yasmeen;Ji, Ling-Xiao;Zhang, Peng-Fei;Zhou, Kai
    • 《FRONTIERS IN SURGERY》
    • 2020年
    • 7卷
    • 期刊

    The transobturator suburethral tape procedure is emerging as a preferred surgical option in the management of stress urinary incontinence. This procedure, also called tension-free vaginal tape transobturator (TVT-O) procedure, has fewer risks of injury to the bladder, similar effectiveness, and shorter surgery duration compared with the older tension-free vaginal tape (TVT) procedure. In this study, we report the case of a female patient with type 2 diabetes mellitus who developed emergency ketoacidosis and severe cellulitis after a TVT-O procedure, which was successfully managed without sling removal and open drainage of abscesses after multi-point puncture drainage, guided by ultrasound and appropriate antibiotic administration. The patient showed appropriate urinary continence with controlled diabetes mellitus 24 months after treatment. In conclusion, cellulitis from the pelvic floor to the associated thigh after TVT-O procedure in a diabetic patient can be managed conservatively if no sling exposure is confirmed. However, these patients should be closely observed and followed up during the perioperative period, especially for synthetic sling use.

    ...
  • 9.多种护理形式延续护理模式在输尿管皮肤造口术后患者中的应用研究

    • 关键词:
    • 膀胱癌;输尿管皮肤造口;延续护理;自我护理能力;生活质量
    • 王晓微;张小珍;吴春燕;肖海鸟;徐晓虹;江海红
    • 《中国现代医生》
    • 2020年
    • 30期
    • 期刊

    目的探讨多种护理形式延续护理在输尿管皮肤造口术后患者中的应用的重要性。方法2016年10月~2018年12月在本院抽取接受输尿管皮肤造口的膀胱癌患者50例作为研究对象,按随机分为对照组和干预组,每组各25例,对照组采取常规出院指导,干预

    ...
  • 排序方式:
  • 2
  • /