MiR-9-enriched mesenchymal stem cells derived exosomes prevent cystitis-induced bladder pain via suppressing TLR4/NLRP3 pathway in interstitial cystitis mice

富含 miR-9 的间充质干细胞衍生的外泌体通过抑制间质性膀胱炎小鼠的 TLR4/NLRP3 通路预防膀胱炎引起的膀胱疼痛

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作者:Xiangrong Cui, Xingyu Bi, Xiuping Zhang, Zhiping Zhang, Qin Yan, Yanni Wang, Xia Huang, Xueqing Wu, Xuan Jing, Hongwei Wang

Background

Inflammatory response of central nervous system is an important component mechanism in the bladder pain of interstitial cystitis/bladder pain syndrome (IC/BPS). Exosomes transfer with microRNAs (miRNA) from mesenchymal stem cell (MSCs) might inhibit inflammatory injury of the central nervous system. Herein, the

Conclusions

This study demonstrated that miR-9-enreched MSCs derived exosomes alleviate neuroinflammaiton and cystitis-induced bladder pain by inhibiting TLR4/NF-κb/NLRP3 signal pathway in interstitial cystitis mice, which is a promising strategy against cystitis-induced bladder pain.

Methods

On the basis of IC/BPS model, we used various techniques including bioinformatics, cell and molecular biology, and experimental zoology, to elucidate the role and molecular mechanism of TLR4 in regulating the activation of NLRP3 inflammasome in bladder pain of IC/BPS, and investigate the mechanism and feasibility of MSC-EVs enriched with miR-9 in the treatment of bladder pain of IC/BPS.

Results

The inflammatory responses in systemic and central derived by TLR4 activation were closely related to the cystitis-induced pelvic/bladder nociception in IC/BPS model. Intrathecal injection of miR-9-enreched MSCs derived exosomes were effective in the treatment of cystitis-induced pelvic/bladder nociception by inhibiting TLR4/NF-κb/NLRP3 signal pathway in central nervous system of IC/BPS mice. Conclusions: This study demonstrated that miR-9-enreched MSCs derived exosomes alleviate neuroinflammaiton and cystitis-induced bladder pain by inhibiting TLR4/NF-κb/NLRP3 signal pathway in interstitial cystitis mice, which is a promising strategy against cystitis-induced bladder pain.

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