Kim, Hyomin Kim, Eun Kyoung Yu, Yeuni Heo, Hye Jin Kim, Dokyoung Cho, Su-Yeon Kwon, Yujin Kim, Won Kyu Kim, Kihun Ko, Dai Sik Kim, Yun Hak 2025-03-19T15:30:50Z 2025-03-19T15:30:50Z 2025-03-19 2025-02 0003-9861 https://pubs.kist.re.kr/handle/201004/151912 Background and aims: Vascular smooth muscle cells are pivotal in atherosclerosis, transitioning from a contractile to a synthetic phenotype, which is associated with increased proliferation and inflammation. FRZB, a Wnt signaling modulator, has been implicated in vascular pathology, but its specific role in vascular smooth muscle cell phenotype modulation is not well understood. This study investigates the role of FRZB in regulating vascular smooth muscle cell phenotypes. Methods: Vascular smooth muscle cell regions were categorized based on FRZB expression levels, and various analyses, including differential gene expression, KEGG pathway analysis, and Disease Ontology analysis, were conducted. FRZB knockdown in human aortic vascular smooth muscle cell was performed using siRNA, followed by assessments of cell migration, proliferation, and phenotype marker expression. Results: FRZB expression was significantly reduced in synthetic type compared to contractile type in both mouse models and human samples. FRZB knockdown in human vascular smooth muscle cells led to increased cell migration and proliferation, alongside decreased expression of contractile markers and increased synthetic markers. Unexpectedly, FRZB knockdown suppressed Wnt signaling. Pathway analysis revealed associations with the PI3K-Akt signaling pathway, focal adhesion, and ECM interactions. Conclusions: Our study highlights FRZB's role in Vascular smooth muscle cell phenotype modulation, showing that reduced FRZB expression correlates with a synthetic phenotype and increased disease markers. FRZB does not enhance Wnt signaling but may regulate vascular smooth muscle cell behavior through alternative pathways. These findings suggest FRZB as a potential therapeutic target for stabilizing vascular smooth muscle cells and managing atherosclerosis. English Academic Press Modulating vascular smooth muscle cell phenotype via Wnt-Independent FRZB pathways Article 10.1016/j.abb.2025.110290 1 Archives of Biochemistry and Biophysics, v.764 Archives of Biochemistry and Biophysics 764 N scie scopus 001397711900001 2-s2.0-85214333838 Biochemistry & Molecular Biology Biophysics Biochemistry & Molecular Biology Biophysics Article EXTRACELLULAR-MATRIX PROLIFERATION GROWTH Frizzled-related protein Vascular smooth muscle cell Atherosclerosis Phenotype modulation Focal adhesion