Novel carbazole attenuates vascular remodeling through STAT3/CIAPIN1 signaling in vascular smooth muscle cells
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 proliferatio...
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| Format: | Article |
| Language: | English |
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Elsevier
2025-03-01
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| Series: | Acta Pharmaceutica Sinica B |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211383524004921 |
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| author | Joo-Hui Han Jong-Beom Heo Hyung-Won Lee Min-Ho Park Jangmi Choi Eun Joo Yun Seongpyo Lee Gyu Yong Song Chang-Seon Myung |
| author_facet | Joo-Hui Han Jong-Beom Heo Hyung-Won Lee Min-Ho Park Jangmi Choi Eun Joo Yun Seongpyo Lee Gyu Yong Song Chang-Seon Myung |
| author_sort | Joo-Hui Han |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-bebebc97d7df4ceabc7f24f964f1bcd6 |
| institution | DOAJ |
| issn | 2211-3835 |
| language | English |
| publishDate | 2025-03-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Acta Pharmaceutica Sinica B |
| spelling | doaj-art-bebebc97d7df4ceabc7f24f964f1bcd62025-08-20T03:07:58ZengElsevierActa Pharmaceutica Sinica B2211-38352025-03-011531463147910.1016/j.apsb.2024.12.035Novel carbazole attenuates vascular remodeling through STAT3/CIAPIN1 signaling in vascular smooth muscle cellsJoo-Hui Han0Jong-Beom Heo1Hyung-Won Lee2Min-Ho Park3Jangmi Choi4Eun Joo Yun5Seongpyo Lee6Gyu Yong Song7Chang-Seon Myung8College of Pharmacy and Research Institute of Pharmaceutical Sciences, Woosuk University, Wanju 55338, Republic of Korea; Corresponding authors.College of Pharmacy, Chungnam National University, Daejeon 34134, Republic of KoreaCollege of Pharmacy, Woosuk University, Wanju 55338, Republic of KoreaInstitute of Drug Research and Development, College of Pharmacy, Chungnam National University, Daejeon 34134, Republic of KoreaInstitute of Drug Research and Development, College of Pharmacy, Chungnam National University, Daejeon 34134, Republic of KoreaCollege of Pharmacy, Chungnam National University, Daejeon 34134, Republic of KoreaCollege of Pharmacy, Woosuk University, Wanju 55338, Republic of KoreaCollege of Pharmacy, Chungnam National University, Daejeon 34134, Republic of Korea; Corresponding authors.Department of Pharmacology, College of Pharmacy, Chungnam National University, Daejeon 34134, Republic of Korea; Corresponding authors.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.http://www.sciencedirect.com/science/article/pii/S2211383524004921AtherosclerosisVascular smooth muscle cellSignal transducer and activator of transcription 3Cytokine induced apoptosis inhibitor 1Janus tyrosine kinase 2Phenotyping switching |
| spellingShingle | Joo-Hui Han Jong-Beom Heo Hyung-Won Lee Min-Ho Park Jangmi Choi Eun Joo Yun Seongpyo Lee Gyu Yong Song Chang-Seon Myung Novel carbazole attenuates vascular remodeling through STAT3/CIAPIN1 signaling in vascular smooth muscle cells Acta Pharmaceutica Sinica B Atherosclerosis Vascular smooth muscle cell Signal transducer and activator of transcription 3 Cytokine induced apoptosis inhibitor 1 Janus tyrosine kinase 2 Phenotyping switching |
| title | Novel carbazole attenuates vascular remodeling through STAT3/CIAPIN1 signaling in vascular smooth muscle cells |
| title_full | Novel carbazole attenuates vascular remodeling through STAT3/CIAPIN1 signaling in vascular smooth muscle cells |
| title_fullStr | Novel carbazole attenuates vascular remodeling through STAT3/CIAPIN1 signaling in vascular smooth muscle cells |
| title_full_unstemmed | Novel carbazole attenuates vascular remodeling through STAT3/CIAPIN1 signaling in vascular smooth muscle cells |
| title_short | Novel carbazole attenuates vascular remodeling through STAT3/CIAPIN1 signaling in vascular smooth muscle cells |
| title_sort | novel carbazole attenuates vascular remodeling through stat3 ciapin1 signaling in vascular smooth muscle cells |
| topic | Atherosclerosis Vascular smooth muscle cell Signal transducer and activator of transcription 3 Cytokine induced apoptosis inhibitor 1 Janus tyrosine kinase 2 Phenotyping switching |
| url | http://www.sciencedirect.com/science/article/pii/S2211383524004921 |
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