The combination of high glucose and LPS induces autophagy in bovine kidney epithelial cells via the Notch3/mTOR signaling pathway

高糖和LPS联合作用通过Notch3/mTOR信号通路诱导牛肾上皮细胞自噬

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作者:Yaocheng Cui #, Hongrui Guo #, Qin Zhang, Jing Fang, Yue Xie, Shiyi Chen, Xiaoping Ma, Liping Gou, Hengmin Cui, Yi Geng, Gang Ye, Zhijun Zhong, Zhihua Ren, Ya Wang, Junliang Deng, Shuming Yu, Suizhong Cao, Zhisheng Wang, Zhicai Zuo

Background

Aside respiratory diseases, beef cattle may also suffer from serious kidney diseases after transportation. Hyperglycemia and gram-negative bacterial infection may be the main reasons why bovine is prone to severe kidney disease during transportation stress, however, the precise mechanism is still unclear. The

Conclusions

This study demonstrated that the combination effect of HG and LPS could induce autophagy in MDBK cells, and the Notch3/mTOR signaling pathway was involved in HG and LPS-induced autophagy.

Results

As we discovered, the combined effect of HG and LPS decreased MDBK cells viability. And, HG and LPS combination also induced autophagy in MDBK cells, which was characterized by increasing the expression of LC3-II/I and Beclin1 and decreasing p62 expression. LC3 fluorescence signal formation was also significantly increased by HG and LPS combination treatment. Furthermore, we measured whether the mammalian target of rapamycin (mTOR) and the Notch3 signaling pathways were involved in HG and LPS-induced autophagy. The results showed that the combination of HG and LPS significantly increased the protein expression of Notch3 and decreased protein expression of p-mTOR, indicating that Notch3 and mTOR signaling pathways were activated. However, co-treatment with the Notch3 inhibitor (DAPT) could reverse the induction of autophagy, and increased the protein expression of p-mTOR. Conclusions: This study demonstrated that the combination effect of HG and LPS could induce autophagy in MDBK cells, and the Notch3/mTOR signaling pathway was involved in HG and LPS-induced autophagy.

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