The geranyl acetophenone tHGA attenuates human bronchial smooth muscle proliferation via inhibition of AKT phosphorylation
Increased airway smooth muscle (ASM) mass is a prominent hallmark of airway remodeling in asthma. Inhaled corticosteroids and long-acting beta2-agonists remain the mainstay of asthma therapy, however are not curative and ineffective in attenuating airway remodeling. The geranyl acetophenone 2,4,6-tr...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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Nature Publishing Group
2018
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| Online Access: | http://psasir.upm.edu.my/id/eprint/74185/ http://psasir.upm.edu.my/id/eprint/74185/1/The%20geranyl%20acetophenone%20tHGA%20attenuates%20human%20bronchial%20smooth%20muscle%20proliferation%20via%20inhibition%20of%20AKT%20phosphorylation.pdf |
| _version_ | 1848857450696933376 |
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| author | Yap, Hui Min Lee, Yu Zhao Harith, Hanis Hazeera Tham, Chau Ling Cheema, Manraj Singh Shaari, Khozirah Israf Ali, Daud Ahmad |
| author_facet | Yap, Hui Min Lee, Yu Zhao Harith, Hanis Hazeera Tham, Chau Ling Cheema, Manraj Singh Shaari, Khozirah Israf Ali, Daud Ahmad |
| author_sort | Yap, Hui Min |
| building | UPM Institutional Repository |
| collection | Online Access |
| description | Increased airway smooth muscle (ASM) mass is a prominent hallmark of airway remodeling in asthma. Inhaled corticosteroids and long-acting beta2-agonists remain the mainstay of asthma therapy, however are not curative and ineffective in attenuating airway remodeling. The geranyl acetophenone 2,4,6-trihydroxy-3-geranyl acetophenone (tHGA), an in-house synthetic non-steroidal compound, attenuates airway hyperresponsiveness and remodeling in murine models of asthma. The effect of tHGA upon human ASM proliferation, migration and survival in response to growth factors was assessed and its molecular target was determined. Following serum starvation and induction with growth factors, proliferation and migration of human bronchial smooth muscle cells (hBSMCs) treated with tHGA were significantly inhibited without any significant effects upon cell survival. tHGA caused arrest of hBSMC proliferation at the G1 phase of the cell cycle with downregulation of cell cycle proteins, cyclin D1 and diminished degradation of cyclin-dependent kinase inhibitor (CKI), p27Kip1. The inhibitory effect of tHGA was demonstrated to be related to its direct inhibition of AKT phosphorylation, as well as inhibition of JNK and STAT3 signal transduction. Our findings highlight the anti-remodeling potential of this drug lead in chronic airway disease. |
| first_indexed | 2025-11-15T11:57:45Z |
| format | Article |
| id | upm-74185 |
| institution | Universiti Putra Malaysia |
| institution_category | Local University |
| language | English |
| last_indexed | 2025-11-15T11:57:45Z |
| publishDate | 2018 |
| publisher | Nature Publishing Group |
| recordtype | eprints |
| repository_type | Digital Repository |
| spelling | upm-741852020-04-13T12:44:21Z http://psasir.upm.edu.my/id/eprint/74185/ The geranyl acetophenone tHGA attenuates human bronchial smooth muscle proliferation via inhibition of AKT phosphorylation Yap, Hui Min Lee, Yu Zhao Harith, Hanis Hazeera Tham, Chau Ling Cheema, Manraj Singh Shaari, Khozirah Israf Ali, Daud Ahmad Increased airway smooth muscle (ASM) mass is a prominent hallmark of airway remodeling in asthma. Inhaled corticosteroids and long-acting beta2-agonists remain the mainstay of asthma therapy, however are not curative and ineffective in attenuating airway remodeling. The geranyl acetophenone 2,4,6-trihydroxy-3-geranyl acetophenone (tHGA), an in-house synthetic non-steroidal compound, attenuates airway hyperresponsiveness and remodeling in murine models of asthma. The effect of tHGA upon human ASM proliferation, migration and survival in response to growth factors was assessed and its molecular target was determined. Following serum starvation and induction with growth factors, proliferation and migration of human bronchial smooth muscle cells (hBSMCs) treated with tHGA were significantly inhibited without any significant effects upon cell survival. tHGA caused arrest of hBSMC proliferation at the G1 phase of the cell cycle with downregulation of cell cycle proteins, cyclin D1 and diminished degradation of cyclin-dependent kinase inhibitor (CKI), p27Kip1. The inhibitory effect of tHGA was demonstrated to be related to its direct inhibition of AKT phosphorylation, as well as inhibition of JNK and STAT3 signal transduction. Our findings highlight the anti-remodeling potential of this drug lead in chronic airway disease. Nature Publishing Group 2018 Article PeerReviewed text en http://psasir.upm.edu.my/id/eprint/74185/1/The%20geranyl%20acetophenone%20tHGA%20attenuates%20human%20bronchial%20smooth%20muscle%20proliferation%20via%20inhibition%20of%20AKT%20phosphorylation.pdf Yap, Hui Min and Lee, Yu Zhao and Harith, Hanis Hazeera and Tham, Chau Ling and Cheema, Manraj Singh and Shaari, Khozirah and Israf Ali, Daud Ahmad (2018) The geranyl acetophenone tHGA attenuates human bronchial smooth muscle proliferation via inhibition of AKT phosphorylation. Scientific Reports, 8. art. no. 16640. Jan-14. ISSN 2045-2322 https://www.nature.com/articles/s41598-018-34847-0.pdf 10.1038/s41598-018-34847-0 |
| spellingShingle | Yap, Hui Min Lee, Yu Zhao Harith, Hanis Hazeera Tham, Chau Ling Cheema, Manraj Singh Shaari, Khozirah Israf Ali, Daud Ahmad The geranyl acetophenone tHGA attenuates human bronchial smooth muscle proliferation via inhibition of AKT phosphorylation |
| title | The geranyl acetophenone tHGA attenuates human bronchial smooth muscle proliferation via inhibition of AKT phosphorylation |
| title_full | The geranyl acetophenone tHGA attenuates human bronchial smooth muscle proliferation via inhibition of AKT phosphorylation |
| title_fullStr | The geranyl acetophenone tHGA attenuates human bronchial smooth muscle proliferation via inhibition of AKT phosphorylation |
| title_full_unstemmed | The geranyl acetophenone tHGA attenuates human bronchial smooth muscle proliferation via inhibition of AKT phosphorylation |
| title_short | The geranyl acetophenone tHGA attenuates human bronchial smooth muscle proliferation via inhibition of AKT phosphorylation |
| title_sort | geranyl acetophenone thga attenuates human bronchial smooth muscle proliferation via inhibition of akt phosphorylation |
| url | http://psasir.upm.edu.my/id/eprint/74185/ http://psasir.upm.edu.my/id/eprint/74185/ http://psasir.upm.edu.my/id/eprint/74185/ http://psasir.upm.edu.my/id/eprint/74185/1/The%20geranyl%20acetophenone%20tHGA%20attenuates%20human%20bronchial%20smooth%20muscle%20proliferation%20via%20inhibition%20of%20AKT%20phosphorylation.pdf |