Knockdown of WDR1 Inhibits Nuclear Translocation of STAT3 to Regulate Smooth Muscle Cell Proliferation and Migration
10.13865/j.cnki.cjbmb.2021.02.1564
- Author:
Ji-Sheng HU
1
;
Xia HUANG
1
;
Ran AN
1
Author Information
1. Institute of Biology and Medicine, College of Life Science and Health, Wuhan University of Science and Technology
- Publication Type:Journal Article
- Keywords:
migration;
nuclear translocation;
proliferation;
signal transducer and activator of transcription 3(STAT3);
smooth muscle cell;
WD repeat domain 1(WDR1)
- From:
Chinese Journal of Biochemistry and Molecular Biology
2021;37(4):533-542
- CountryChina
- Language:Chinese
-
Abstract:
Nuclear transport of signal transducer and activator of transcription 3 (STAT3) is a prerequisite for its biological function. WD Repeat domain 1 (WDR1), a regulator of the cytoskeleton factors, may affect STAT3 nuclear translocation. However, the molecular mechanism regarding the effect of WDR1 on STAT3 nuclear translocation is still unknown. To investigate the effect of WDR1 on STAT3 nuclear translocation in smooth muscle cells, a human aortic vascular smooth muscle cells (HAVSMCs) model with stable knockdown of WDR1 was constructed. The results of RT-qPCR and Western blot showed that the activation and expression of STAT3 were not significantly altered after knockdown of Wdr1 (P>0. 05); the results of nucleoplasm isolation showed that the nucleoplasm distribution of STAT3 was significantly affected after knockdown of WDR1 compared with the control group. Subsequent results showed that the expression of STAT3 nuclear input-associated protein β (importin β) was inhibited (P < 0. 05) and the nucleoplasmic ratio of Ras-associated nuclear protein (Ran) was significantly decreased compared to the control group. Results from CCK8 and Transwell assays indicated that overexpression of importin β was able to rescue the inhibition of proliferation and migration of HAVSMCs caused by WDR1 knockdown. Further results showed that knockdown of WDR1 resulted in a significant decrease in the expression of nuclear transport factor 2 (NTF2) associated with the Ran nucleotide cycle (P<0. 05). After overexpression of NTF2, the results of CCK8 and Transwell experiments showed that the proliferation and migration ability of HAVSMCs were significantly enhanced (P < 0. 05). Summarizing the above results, knockdown of WDR1, by inhibiting the expression of importin β and NTF2, alters the nucleoplasmic distribution of Ran and decreases the nuclear translocation of STAT3, thus regulating the proliferation and migration of smooth muscle cells.
