High-selective HDAC6 inhibitor alleviates bone marrow fibrosis through inhibiting collagen formation and extracellular matrix deposition
Abstract Bone marrow fibrosis (BMF) impairs normal hematopoietic functions in patients. The overactivation of the TGF-β signaling pathway is regarded as one of the offenders causing disease progression. Thus, factors capable of regulating TGF-β secretion hold great potential in reversing fibrotic di...
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Nature Portfolio
2025-08-01
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| Online Access: | https://doi.org/10.1038/s41598-025-08384-6 |
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| author | Chiao-Hsu Ke Mao-En Huang Hsin-Yi Wu Chao-Wu Yu Shuei-Liong Lin Shau-Ping Lin Shu-Han Yu Chih-Hung Huang Chen-Si Lin |
| author_facet | Chiao-Hsu Ke Mao-En Huang Hsin-Yi Wu Chao-Wu Yu Shuei-Liong Lin Shau-Ping Lin Shu-Han Yu Chih-Hung Huang Chen-Si Lin |
| author_sort | Chiao-Hsu Ke |
| collection | DOAJ |
| description | Abstract Bone marrow fibrosis (BMF) impairs normal hematopoietic functions in patients. The overactivation of the TGF-β signaling pathway is regarded as one of the offenders causing disease progression. Thus, factors capable of regulating TGF-β secretion hold great potential in reversing fibrotic diseases. One such factor is histone deacetylase inhibitors (HDACis), which can modulate the expression of TGF-β. Our previous study successfully synthesized a selective HDAC6 inhibitor, J22352, for pulmonary fibrosis; however, the treatment efficacies on BMF remain unclear. Therefore, in this study, we treated bone marrow-derived myofibroblasts with J22352. The results showed that J22352 significantly reduced cell viability, induced apoptosis, and inhibited extracellular matrix (ECM) accumulation. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis was employed to disclose potential mechanisms, identifying 334 differentially expressed proteins (DEPs). The DEPs were involved in cell apoptosis, programmed cell death, ECM deposition, and collagen formation. These results suggest that J22352 efficiently alleviated BMF by inducing cell apoptosis and inhibiting ECM deposition. This study introduces a novel selective HDAC6 inhibitor as a potential option for slowing down the progression of BMF. We aim to provide a promising selective HDACi for clinical medicine through a detailed analysis of its mechanisms and efficacy, offering new prospects in the field. |
| format | Article |
| id | doaj-art-f09a9fbc3a014332b89e02e3d0b608b5 |
| institution | Kabale University |
| issn | 2045-2322 |
| language | English |
| publishDate | 2025-08-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj-art-f09a9fbc3a014332b89e02e3d0b608b52025-08-20T04:01:51ZengNature PortfolioScientific Reports2045-23222025-08-0115111410.1038/s41598-025-08384-6High-selective HDAC6 inhibitor alleviates bone marrow fibrosis through inhibiting collagen formation and extracellular matrix depositionChiao-Hsu Ke0Mao-En Huang1Hsin-Yi Wu2Chao-Wu Yu3Shuei-Liong Lin4Shau-Ping Lin5Shu-Han Yu6Chih-Hung Huang7Chen-Si Lin8Department of Veterinary Medicine, School of Veterinary Medicine, National Taiwan UniversityDepartment of Veterinary Medicine, School of Veterinary Medicine, National Taiwan UniversityInstrumentation Center, National Taiwan UniversitySchool of Pharmacy, College of Medicine, National Taiwan UniversityGraduate Institute of Physiology, College of Medicine, National Taiwan UniversityAgricultural Biotechnology Research Center, Academia SinicaInstitute of Biotechnology, National Taiwan UniversityDepartment of Chemical Engineering and Biotechnology, Institute of Chemical Engineering, National Taipei University of TechnologyDepartment of Veterinary Medicine, School of Veterinary Medicine, National Taiwan UniversityAbstract Bone marrow fibrosis (BMF) impairs normal hematopoietic functions in patients. The overactivation of the TGF-β signaling pathway is regarded as one of the offenders causing disease progression. Thus, factors capable of regulating TGF-β secretion hold great potential in reversing fibrotic diseases. One such factor is histone deacetylase inhibitors (HDACis), which can modulate the expression of TGF-β. Our previous study successfully synthesized a selective HDAC6 inhibitor, J22352, for pulmonary fibrosis; however, the treatment efficacies on BMF remain unclear. Therefore, in this study, we treated bone marrow-derived myofibroblasts with J22352. The results showed that J22352 significantly reduced cell viability, induced apoptosis, and inhibited extracellular matrix (ECM) accumulation. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis was employed to disclose potential mechanisms, identifying 334 differentially expressed proteins (DEPs). The DEPs were involved in cell apoptosis, programmed cell death, ECM deposition, and collagen formation. These results suggest that J22352 efficiently alleviated BMF by inducing cell apoptosis and inhibiting ECM deposition. This study introduces a novel selective HDAC6 inhibitor as a potential option for slowing down the progression of BMF. We aim to provide a promising selective HDACi for clinical medicine through a detailed analysis of its mechanisms and efficacy, offering new prospects in the field.https://doi.org/10.1038/s41598-025-08384-6Bone marrow fibrosisHistone deacetylase inhibitorTransforming growth factor-β (TGF-β)Organ fibrosis |
| spellingShingle | Chiao-Hsu Ke Mao-En Huang Hsin-Yi Wu Chao-Wu Yu Shuei-Liong Lin Shau-Ping Lin Shu-Han Yu Chih-Hung Huang Chen-Si Lin High-selective HDAC6 inhibitor alleviates bone marrow fibrosis through inhibiting collagen formation and extracellular matrix deposition Scientific Reports Bone marrow fibrosis Histone deacetylase inhibitor Transforming growth factor-β (TGF-β) Organ fibrosis |
| title | High-selective HDAC6 inhibitor alleviates bone marrow fibrosis through inhibiting collagen formation and extracellular matrix deposition |
| title_full | High-selective HDAC6 inhibitor alleviates bone marrow fibrosis through inhibiting collagen formation and extracellular matrix deposition |
| title_fullStr | High-selective HDAC6 inhibitor alleviates bone marrow fibrosis through inhibiting collagen formation and extracellular matrix deposition |
| title_full_unstemmed | High-selective HDAC6 inhibitor alleviates bone marrow fibrosis through inhibiting collagen formation and extracellular matrix deposition |
| title_short | High-selective HDAC6 inhibitor alleviates bone marrow fibrosis through inhibiting collagen formation and extracellular matrix deposition |
| title_sort | high selective hdac6 inhibitor alleviates bone marrow fibrosis through inhibiting collagen formation and extracellular matrix deposition |
| topic | Bone marrow fibrosis Histone deacetylase inhibitor Transforming growth factor-β (TGF-β) Organ fibrosis |
| url | https://doi.org/10.1038/s41598-025-08384-6 |
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