2. Academic Validation
  3. circFAM53B-1 and circFAM53B-2 drive VSMC phenotypic modulation via ISG15-mediated suppression of SRF

circFAM53B-1 and circFAM53B-2 drive VSMC phenotypic modulation via ISG15-mediated suppression of SRF

  • Cell Signal. 2026 Jul:143:112498. doi: 10.1016/j.cellsig.2026.112498.
Lingdan Zhao 1,  Yan Li 1,  Ran Bi 1,  Jiayi Shen 2,  Yingbo Gao 1,  Junhuai Song 1,  Zekun Zhen 3,  Bin Zheng 1,  Hongguang Lian 4,  Jinkun Wen 5,  Xinhua Zhang 6
Affiliations

Affiliations

  • 1 Department of Biochemistry and Molecular Biology, Key Laboratory of Neural and Vascular Biology, Ministry of Education, Hebei Medical University, Shijiazhuang 050017, China.
  • 2 Jiangsu Health Vocational College, Nanjing 211800, China.
  • 3 Hebei Chest Hospital, Shijiazhuang 050041, China.
  • 4 Department of Pathology, The Second Hospital of Hebei Medical University, Shijiazhuang 050000, China.
  • 5 Department of Biochemistry and Molecular Biology, Key Laboratory of Neural and Vascular Biology, Ministry of Education, Hebei Medical University, Shijiazhuang 050017, China. Electronic address: [email protected].
  • 6 Department of Biochemistry and Molecular Biology, Key Laboratory of Neural and Vascular Biology, Ministry of Education, Hebei Medical University, Shijiazhuang 050017, China; Key Laboratory of Tranquilizing TCM, Hebei Provincial Administration of Traditional Chinese Medicine, Shijiazhuang 050017, China. Electronic address: [email protected].
PMID: 41861925 DOI: 10.1016/j.cellsig.2026.112498
Abstract

Although circRNAs have been widely studied in various disease contexts, their roles in vascular smooth muscle cells (VSMCs) phenotypic modulation remain incompletely understood. This study aims to investigate the regulatory functions and molecular mechanisms of two newly identified circRNAs, circFAM53B-1 and circFAM53B-2, in VSMCs phenotypic switching. Here, we show that both circFAM53B-1 and circFAM53B-2 were upregulated by PDGF-BB in a KLF4-dependent manner. They decreased VSMCs contractile markers α-SMA and SM22α levels by suppressing the expression of serum response factor (SRF). Mechanistically, the PDGF-BB-KLF4-circFAM53B1/2 axis enhanced ISG15 expression, which in turn promoted SRF degradation via the ubiquitin-proteasome pathway, subsequently facilitating VSMCs phenotype switching. This study identifies circFAM53B-1 and circFAM53B-2 as key regulators of VSMCs phenotypic switching via the ISG15-SRF pathway. These findings provide new insights into the molecular mechanisms underlying vascular remodeling and suggest potential therapeutic targets for related diseases. Further research is needed to clarify the precise regulation of ISG15 by circFAM53B-1/2 and to evaluate their in vivo therapeutic potential.

Keywords

ISG15; KLF4; VSMCs phenotype switching; circFAM53B-1/2.

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