Effects of Kindlin-2 on proliferation and migration of VSMC and integrinβ1 andβ3 activity via FAK-PI3K signaling pathway.

Xiaolin Wu,Fang Bian,Tongjian Zhu,Qing Zhou,He Hu,Chenyu Li,Salvatore V Pizzo

doi:10.1371/journal.pone.0225173

Xiaolin Wu, Fang Bian + Show 5 more

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https://doi.org/10.1371/journal.pone.0225173

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Abstract

Vascular hyperplasia after vascular trauma is one of the difficult problems in clinical treatment. Nowadays, there is no effective treatment for vascular hyperplasia. Previous studies have shown that integrinβ1 andβ3 activity play an important role in vascular hyperplasia. Kindlin-2 has been shown to modulate integrinβ1 andβ3 activity in cancer. Therefore, in this study, we hope to explore the relationship between Kindlin-2 and vascular hyperplasia. We overexpressed or knocked down Kindlin-2 by adenovirus. The results showed that Kindlin-2 overexpression could regulate integrinβ1 andβ3 activity through FAK-PIK3 signaling pathways ex vivo and in vivo, thereby affecting the proliferation and migration of VSMC, and then it causes the consequences of vascular hyperplasia. Therefore, Our results show that Kindlin-2 may be a potential target for the treatment of vascular hyperplasia.

Highlights

Intimal hyperplasia is a typical feature after vascular injury
The results showed that all the cells we isolated were highly expressed in α-SMA, which indicated that the cells we isolated were VSMC (Fig 1A)
We found that the overexpression of Kindlin-2 promoted intimal hyperplasia, which was caused by the proliferation or migration of VSMCs, compared with the control group and the mock group (Fig 5B)

Summary

Introduction

Intimal hyperplasia is a typical feature after vascular injury. Endometrial hyperplasia is a chronic vascular wall structural change, accompanied by a variety of inflammatory factors, cytokines, chemokines secretion, thereby promoting vascular smooth muscle cell(VSMC) migration, proliferation, and secretion of extracellular matrix of a pathophysiological process [1]. The blood vessels will respond, which will last for weeks or even months. During this process, intimal hyperplasia will occur. This process mainly involves 3 factors: vascular smooth muscle cells, endothelial cells and extracellular matrix [2]. The proliferation and migration of vascular smooth muscle cells are the main pathological features of intimal hyperplasia

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Conclusion