Noncanonical Activin A Signaling in PC12 Cells: A Self-Limiting Feedback Loop

作者：Wang, Jiao-Qi; Liang, Wen-Zhao; Cui, Yang; He, Jin-Ting; Liu, Hong-Yu; Wang, Yue; Xue, Long-Xing; Ji, Qiu-Ye; Shi, Wei; Shao, Yan-Kun; Mang, Jing^*; Xu, Zhong-Xin^*

来源：Neurochemical Research, 2016, 41(5): 1073-1084.

DOI：10.1007/s11064-015-1797-5

• Activin A
• Signaling loop
• Smad anchor for receptor activation

Activin A (Act A), a member of transforming growth factor-beta superfamily, plays a neuroprotective role in multiple neurological diseases through Act A/Smads signal activation. Traditionally, the up-regulation of Act A gene and extracellular Act A accumulation show the signal activation as a linear pathway. However, one of our discoveries indicated that Act A could lead a loop signaling in ischemic injury. To clarify the characteristic of this loop signaling in a non-pathological state, we up-regulated the expression of Act A, monitored extracellular Act A accumulation and examined the activity of Act A signaling, which was quantified by the expression of phosphorylated Smad3 and the fluorescence intensity of Smad4 in nuclei. The results demonstrated a noncanonical Act A signal loop with self-amplifying property in PC12 cells. Further, it showed self-limiting behavior due to temporary activation and spontaneous attenuation. This periodic behavior of Act A signal loop was found to be regulated by the level of Smad anchor for receptor activation (SARA). Moreover, increased activity of Act A signal loop could promote PC12 cell proliferation and enhance the survival rate of cells to Oxygen-Glucose Deprivation. These practical discoveries will bring new insight on the functional outcome of Act A signaling in neurological diseases by the further understanding: loop signaling.

• 出版日期2016-5
• 单位吉林大学