Cysteine and glycine-rich protein 2 promotes hypoxic pulmonary vascular smooth muscle cell proliferation through the Wnt3α-β-catenin/lymphoid enhancer-binding factor 1 pathway.

Liyu Tang, Nan Wang, Xiaozhen Wei, Sirui Huang, Pan Wang, Yameng Zheng, Liangwan Chen, Li Zhang

Journal of biochemical and molecular toxicology 2022 Sep

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Pulmonary hypertension (PH) is mainly characterized by abnormal pulmonary vascular hyperplasia and vascular remodeling, but its mechanism is complicated and currently unclear. Cysteine and glycine-rich protein 2 (Csrp2) has been reported to promote cell proliferation and migration, and affect cell cycle progression. As a new invasive actin-binding factor, Csrp2 increased the invasion and even metastasis of some cancer cells. It was associated with tumor recurrence and chemotherapy resistance. However, the role of Csrp2 in PH remains unknown. We found that Csrp2 expression was increased both in pulmonary arteries (PAs) and smooth muscle cells (PASMCs) in PH. Csrp2 enhanced PASMC proliferation and phenotypic transition. The Wnt3α-β-catenin/lymphoid enhancer-binding factor 1 (LEF1) pathway is involved in cell proliferation and phenotypic transition regulated by Csrp2 expression. These results suggest that hypoxia downregulates YinYang-1 (YY1) and then increases Csrp2 expression. Increased Csrp2 promotes PASMC proliferation and phenotypic transition by activating the Wnt3α-β-catenin/LEF1 pathways, which leads to pulmonary vascular remodeling and even provides a new theoretical basis for studying the pathogenesis and therapeutic targets of PH. © 2022 Wiley Periodicals LLC.

Citation

Liyu Tang, Nan Wang, Xiaozhen Wei, Sirui Huang, Pan Wang, Yameng Zheng, Liangwan Chen, Li Zhang. Cysteine and glycine-rich protein 2 promotes hypoxic pulmonary vascular smooth muscle cell proliferation through the Wnt3α-β-catenin/lymphoid enhancer-binding factor 1 pathway. Journal of biochemical and molecular toxicology. 2022 Sep;36(9):e23122