Bone Marrow Mesenchymal Stem Cell-Derived Exosomes Ameliorate Aging-Induced BTB Impairment in Porcine Testes by Activating Autophagy and Inhibiting ROS/NLRP3 Inflammasomes via the AMPK/mTOR Signaling Pathway

被引：6

作者：

Zhou, Yi ^{[1
]}

Yan, Jiale ^{[1
]}

Qiao, Limin ^{[2
]}

Zeng, Jiaqin ^{[1
]}

Cao, Fuyu ^{[1
]}

Sheng, Xihui ^{[1
]}

Qi, Xiaolong ^{[1
]}

Long, Cheng ^{[1
]}

Liu, Bingying ^{[1
]}

Wang, Xiangguo ^{[1
]}

Yao, Hua ^{[1
]}

Xiao, Longfei ^{[1
]}

机构：

[1] Beijing Univ Agr, Anim Sci & Technol Coll, Beijing 102206, Peoples R China

[2] Beijing Vocat Coll Agr, Dept Anim Husb & Vet, Beijing 102445, Peoples R China

来源：

ANTIOXIDANTS | 2024年 / 13卷 / 02期

关键词：

senescence; blood-testis barrier; BMSC-Exos; autophagy; tight junction; OXIDATIVE STRESS;

D O I：

10.3390/antiox13020183

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

As a pivotal player in spermatogenesis, the blood-testis barrier (BTB) made from junction apparatus coexisting in Sertoli cells (SCs) is impaired with an increase in age and ultimately induces spermatogenic dysfunction or even infertility. It has been corroborated that bone marrow mesenchymal stem cell (BMSC) transplantation can efficiently repair and regenerate the testicular function. As vital mediators of cell-to-cell communication, MSC-derived exosomes (Exos) can directly serve as therapeutic agents for tissue repair and regeneration. However, the therapeutic value of BMSC-Exos in aging-induced BTB damage remains to be confirmed. In this study, we explored that the old porcine testes had defective autophagy, which aggravated BTB disruption in SCs. BMSC-Exos could decrease ROS production and NLRP3 inflammasome activation but enhanced autophagy and tight junction (TJ) function in D-gal-triggered aging porcine SCs and mouse model testes, according to in vitro and in vivo experiments. Furthermore, rapamycin, NAC, MCC950, and IL-1Ra restored the TJ function in D-gal-stimulated aging porcine SCs, while BMSC-Exos' stimulatory effect on TJ function was inhibited by chloroquine. Moreover, the treatment with BMSC-Exos enhanced autophagy in D-gal-induced aging porcine SCs by means of the AMPK/mTOR signal transduction pathway. These findings uncovered through the present study that BMSC-Exos can enhance the BTB function in aging testes by improving autophagy via the AMPK/mTOR signaling pathway, thereby suppressing ROS production and NLRP3 inflammasome activation.

引用

页数：19