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Knockdown of microRNA-17-5p Enhances the Neuroprotective Effect of Act A/Smads Signal Loop After Ischemic Injury

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Abstract

Cerebral ischemic injury is a leading cause of human mortality and disability, seriously threatening human health in the world. Activin A (Act A), as a well-known neuroprotective factor, could alleviate ischemic brain injury mainly through Act A/Smads signaling. In our previous study, a noncanonical Act A/Smads signal loop with self-amplifying property was found, which strengthened the neuroprotective effect of Act A. However, this neuroprotective effect was limited due to the self-limiting behavior mediated by Smad anchor for receptor activation (SARA) protein. It was reported that microRNA-17-5p (miR-17-5p) could suppress the expression of SARA in esophageal squamous cell carcinoma. Thus we proposed that knockdown of miR-17-5p could strengthen the neuroprotective effect of Act A/Smads signal loop through SARA. To testify this hypothesis, oxygen–glucose deficiency (OGD) was introduced to highly differentiated rattus pheochromocytoma (PC12) cells. After the transfection of miR-17-5p mimic or inhibitor, the activity of Act A signal loop was quantified by the expression of phosphorylated Smad3. The results showed that suppression of miR-17-5p up-regulated the expression of SARA protein, which prolonged and strengthened the activity of Act A signaling through increased phosphorylation of downstream Smad3 and accumulation of Act A ligand. Further luciferase assay confirmed that SARA was a direct target gene of miR-17-5p. These practical discoveries will bring new insight on the endogenous neuroprotective effects of Act A signal loop by interfering a novel target: miR-17-5p.

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Acknowledgements

This work was supported by the National Natural Science Foundation of China (81671159), the National Natural Science Foundation of China (31700927) and Jilin Province Science and Technology Development Project (20190103081JH).

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Authors and Affiliations

  1. Department of Neurology, China-Japan Union Hospital, Jilin University, 126 **antai Street, Changchun, 130012, China

    Jiao-Qi Wang, Yue Dong, Hong-Yu Liu, Yu-Kai Wang, Lei Xu, Jia-Hui Yang, Yun-**a Cui, **-Ting He, **g Mang & Zhong-**n Xu

  2. Department of Clinical Medicine, College of Clinical Medicine, Bethune Medicine Institute, Jilin University, 828 **nmin Street, Changchun, 130012, China

    Si-Jia Li & Cheng-Liang Pan

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  1. Jiao-Qi Wang
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Correspondence to Zhong-**n Xu.

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Wang, JQ., Dong, Y., Li, SJ. et al. Knockdown of microRNA-17-5p Enhances the Neuroprotective Effect of Act A/Smads Signal Loop After Ischemic Injury. Neurochem Res 44, 1807–1817 (2019). https://doi.org/10.1007/s11064-019-02815-3

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  • DOI: https://doi.org/10.1007/s11064-019-02815-3

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