<p>Downregulation of miR-200a Protects Mouse Leydig Cells Against Triptolide by Triggering Autophagy</p>

Abstract

Background MicroRNAs play important roles in testicular development and spermatogenesis. Previous research has indicated that the level of miR-200a was significantly upregulated in patients with different spermatogenic impairments. However, the mechanism by which miR-200a regulated spermatogenic impairments remains unclear. Methods Leydig cells were treated with triptolide (TP) to mimic spermatogenic impairments. CCK-8 and flow cytometry were used to detect the proliferation and apoptosis in Leydig cells, respectively. In addition, Western blot assay was used to examine ATG7, ATG5, p62 protein levels in MLTC-1 cells. Results TP dose-dependently upregulated the expression of miR-200a in MLTC-1 cells. In addition, TP inhibited the proliferation of MLTC-1 cells via inducing apoptosis and oxidative stress; however, these phenomena were notably reversed by miR-200a antagomir. Furthermore, luciferase reporter assay identified that ATG7 was the direct binding target of miR-200a. TP treatment markedly inhibited the activation of autophagy in MLTC-1 cells via inhibition of ATG7. Conversely, downregulation of miR-200a significantly induced autophagy in TP-treated MLTC-1 cells by activation of ATG7. Meanwhile, the cell protective effects of miR-200a against TP were reversed by autophagy inhibitor 3MA, indicating that autophagy plays an important role. Conclusion These results indicated that downregulation of miR-200a could protect MLTC-1 cells against TP by inducing autophagy. Therefore, miR-200a might serve as a new therapeutic target for the treatment of male hypogonadism.

Triptolide Induces Leydig Cell Apoptosis by Disrupting Mitochondrial Dynamics in Rats

“…In addition, triptolide increased miR-26a expression in rat Leydig cells, which decreased GSk 3β mRNA levels and inhibited testosterone production ( Liang et al, 2019 ). Another study also reported that triptolide induced Leydig cell apoptosis, and this effect might be highly associated with miR-200 ( Miao et al, 2020 ). These results suggested that miRNAs might play an important role in triptolide-induced Leydig cell apoptosis.…”

Autophagy, a critical element in the aging male reproductive disorders and prostate cancer: a therapeutic point of view

“…For example, the microRNA miR-200a is upregulated in patients with spermatogenesis disorders. ATG7 was identified as a direct binding target of this microRNA [ 61 ]. Interestingly, triptolide (TP), a diterpenoid triepoxide, can increase the expression of miR-200a in the MLTC-1 Leydig cell line and suppress autophagy in these cells.…”

Neuroprotection of Triptolide against Amyloid-Beta1-42-induced toxicity via the Akt/mTOR/p70S6K-mediated Autophagy Pathway

“…Triptolide (TP) is the primary active compound in the Traditional Chinese Medicine (TCM) herb Tripterygium wilfordii Hook F. (TWHF), which possesses a diverse range of immunosuppressive and anti-inflammatory properties . Multiple studies have shown that triptolide is an autophagy modulator and its activity is associated with the up-or down-regulation autophagy (Chan et al 2017, Li et al 2017b, Miao et al 2020, Xie et al 2019. Because of its neuroprotective effects, the therapeutic potential of triptolide for AD has attracted significant attention (Li & Hao 2019).…”