Dataset Information

RNA Splicing of the Abi1 Gene by MBNL1 contributes to macrophage-like phenotype modulation of vascular smooth muscle cell during atherogenesis.

ABSTRACT:

Background

Vascular smooth muscle cells (VSMC) switch to macrophage-like cells after cholesterol loading, and this change may play an important role in atherogenesis. Muscleblind-like splicing regulator 1 (MBNL1) is a well-known splicing factor that has been implicated in many cellular processes. However, the role of MBNL1 in VSMC macrophage-like transdifferentiation is largely unknown. In this study, we aim to characterize the role of MBNL1-induced gene splicing during atherogenesis.

Methods

The expression of MBNL1 and Abelson interactor 1 (Abi1) splice variants (Abi1-e10 and Abi1-Δe10) was compared between artery tissues from healthy donors and atherosclerosis patients. Regulatory mechanisms of MBNL1-induced Abi1 gene splicing were studied, and the signal pathways mediated by Abi1 splice variants were investigated in VSMC.

Results

Loss of MBNL1 was found in the macrophage-like VSMC (VSMC-M) in artery wall from atherosclerosis patients. In vitro and in vivo evidence confirmed that Abi1 is one of the MBNL1 target genes. Loss of MBNL1 significantly induces the Abi1-Δe10 isoform expression. Compared to the known actin organization activities of the Abi1 gene, we discovered a novel action of Abi1-Δe10, whereby Abi1-Δe10 activates Rac1 independent of upstream stimulation and triggers the Rac1-NOX1-ROS pathway, which results in increased expression of transcription factor Kruppel-like factor 4 (KLF4). While Abi1-Δe10 inhibits contractile VSMC biomarkers expression and cell contraction, it stimulates VSMC proliferation, migration and macrophage-like transdifferentiation.

Conclusion

Loss-of-function of MBNL1 activates VSMC-M transdifferentiation to promote atherogenesis through regulating Abi1 RNA splicing.

SUBMITTER: Li Y

PROVIDER: S-EPMC8088461 | biostudies-literature | 2021 May

REPOSITORIES: biostudies-literature

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Publications

RNA Splicing of the Abi1 Gene by MBNL1 contributes to macrophage-like phenotype modulation of vascular smooth muscle cell during atherogenesis.

Li Yinan Y Guo Xiangjiang X Xue Guanhua G Wang Han H Wang Yuli Y Wang Weilun W Yang Shuofei S Ni Qihong Q Chen Jiaquan J Lv Lei L Zhao Yiping Y Ye Meng M Zhang Lan L

Cell proliferation 20210323 5

<h4>Background</h4>Vascular smooth muscle cells (VSMC) switch to macrophage-like cells after cholesterol loading, and this change may play an important role in atherogenesis. Muscleblind-like splicing regulator 1 (MBNL1) is a well-known splicing factor that has been implicated in many cellular processes. However, the role of MBNL1 in VSMC macrophage-like transdifferentiation is largely unknown. In this study, we aim to characterize the role of MBNL1-induced gene splicing during atherogenesis.<h4 ...[more]

PMID: 33759281

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Dataset Information

RNA Splicing of the Abi1 Gene by MBNL1 contributes to macrophage-like phenotype modulation of vascular smooth muscle cell during atherogenesis.

Background

Methods

Results

Conclusion

Publications

RNA Splicing of the Abi1 Gene by MBNL1 contributes to macrophage-like phenotype modulation of vascular smooth muscle cell during atherogenesis.

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