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충남대학교

Acta Pharm. Sin. B, Available online 3 January 2025 | https://doi.org/10.1016/j.apsb.2024.12.035 Novel carbazole attenuates vascular remodeling through STAT3/CIAPIN1 signaling in vascular smooth muscle cells

Joo-Hui Han ^a, Jong-Beom Heo ^b, Hyung-Won Lee^c, Min-Ho Park^d, Jangmi Choi^d, Eun Joo Yun ^b, Seongpyo Lee ^c, Gyu Yong Song ^b, Chang-Seon Myung^e

^aCollege of Pharmacy and Research Institute of Pharmaceutical Sciences, Woosuk University, Wanju 55338, Republic of Korea
^bCollege of Pharmacy, Chungnam National University, Daejeon 34134, Republic of Korea
^cCollege of Pharmacy, Woosuk University, Wanju 55338, Republic of Korea
^dInstitute of Drug Research and Development, College of Pharmacy, Chungnam National University, Daejeon 34134, Republic of Korea
^eDepartment of Pharmacology, College of Pharmacy, Chungnam National University, Daejeon 34134, Republic of Korea

Corresponding authors: Joo-Hui Han, Gyu Yong Song, Chang-Seon Myung

Abstract

This study investigated the molecular mechanism of phenotypic switching of vascular smooth muscle cells (VSMCs), which play a crucial role in vascular remodeling using 9H-carbazol-3-yl-4-aminobenzoate (CAB).CAB significantly attenuated platelet-derived growth factor (PDGF)-induced VSMC proliferation and migration. CAB suppressed PDGF-induced STAT3 activation by directly binding to the SH2 domain of STAT3. Downregulation of STAT3 phosphorylation by CAB attenuated CIAPIN1/JAK2/STAT3 axis through a decrease in CIAPIN1 transcription. Furthermore, abrogated CIAPIN1 decreased KLF4-mediated VSMC dedifferentiation and increased CDKN1B-induced cell cycle arrest and MMP9 suppression. CAB inhibited intimal hyperplasia in injury-induced neointima animal models by inhibition of the CIAPIN1/JAK2/STAT3 axis. However, CIAPIN1 overexpression attenuated CAB-mediated suppression of VSMC proliferation, migration, phenotypic switching, and intimal hyperplasia. Our study clarified the molecular mechanism underlying STAT3 inhibition of VSMC phenotypic switching and vascular remodeling and identified novel active CAB. These findings demonstrated that STAT3 can be a major regulator to control CIAPIN1/JAK2/STAT3 axis that may be a therapeutic target for treating vascular proliferative diseases.

논문정보

형식Research article
게재일2025년 01월 (BRIC 등록일 2025-01-06)
연구진국내 연구진
분야 의약학 > 약리의학

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