Rosemary Extract-Induced Autophagy and Decrease in Accumulation of Collagen Type I in Osteogenesis Imperfecta Skin Fibroblasts
Osteogenesis imperfecta (OI) is a heterogeneous connective tissue disease mainly caused by structural mutations in type I collagen. Mutant collagen accumulates intracellularly, causing cellular stress that has recently been shown to be phenotype-related. Therefore, the aim of the study was to search...
| Main Authors: | , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2022-09-01
|
| Series: | International Journal of Molecular Sciences |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1422-0067/23/18/10341 |
| _version_ | 1797487459149283328 |
|---|---|
| author | Joanna Sutkowska-Skolimowska Justyna Brańska-Januszewska Jakub W. Strawa Halina Ostrowska Malwina Botor Katarzyna Gawron Anna Galicka |
| author_facet | Joanna Sutkowska-Skolimowska Justyna Brańska-Januszewska Jakub W. Strawa Halina Ostrowska Malwina Botor Katarzyna Gawron Anna Galicka |
| author_sort | Joanna Sutkowska-Skolimowska |
| collection | DOAJ |
| description | Osteogenesis imperfecta (OI) is a heterogeneous connective tissue disease mainly caused by structural mutations in type I collagen. Mutant collagen accumulates intracellularly, causing cellular stress that has recently been shown to be phenotype-related. Therefore, the aim of the study was to search for potential drugs reducing collagen accumulation and improving OI fibroblast homeostasis. We found that rosemary extract (RE), which is of great interest to researchers due to its high therapeutic potential, at concentrations of 50 and 100 µg/mL significantly reduced the level of accumulated collagen in the fibroblasts of four patients with severe and lethal OI. The decrease in collagen accumulation was associated with RE-induced autophagy as was evidenced by an increase in the LC3-II/LC3-I ratio, a decrease in p62, and co-localization of type I collagen with LC3-II and LAMP2A by confocal microscopy. The unfolded protein response, activated in three of the four tested cells, and the level of pro-apoptotic markers (Bax, CHOP and cleaved caspase 3) were attenuated by RE. In addition, the role of RE-modulated proteasome in the degradation of unfolded procollagen chains was investigated. This study provides new insight into the beneficial effects of RE that may have some implications in OI therapy targeting cellular stress. |
| first_indexed | 2024-03-09T23:47:57Z |
| format | Article |
| id | doaj.art-a1155f9924e54999854daeddd9eba553 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-09T23:47:57Z |
| publishDate | 2022-09-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-a1155f9924e54999854daeddd9eba5532023-11-23T16:39:57ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672022-09-0123181034110.3390/ijms231810341Rosemary Extract-Induced Autophagy and Decrease in Accumulation of Collagen Type I in Osteogenesis Imperfecta Skin FibroblastsJoanna Sutkowska-Skolimowska0Justyna Brańska-Januszewska1Jakub W. Strawa2Halina Ostrowska3Malwina Botor4Katarzyna Gawron5Anna Galicka6Department of Medical Chemistry, Medical University of Bialystok, Mickiewicza 2A, 15-222 Bialystok, PolandDepartment of Biology, Medical University of Bialystok, Mickiewicza 2A, 15-222 Bialystok, PolandDepartment of Pharmacognosy, Medical University of Bialystok, Mickiewicza 2A, 15-230 Bialystok, PolandDepartment of Biology, Medical University of Bialystok, Mickiewicza 2A, 15-222 Bialystok, PolandDepartment of Molecular Biology and Genetics, Faculty of Medical Sciences in Katowice, Medical University of Silesia, Medykow 18, 40-475 Katowice, PolandDepartment of Molecular Biology and Genetics, Faculty of Medical Sciences in Katowice, Medical University of Silesia, Medykow 18, 40-475 Katowice, PolandDepartment of Medical Chemistry, Medical University of Bialystok, Mickiewicza 2A, 15-222 Bialystok, PolandOsteogenesis imperfecta (OI) is a heterogeneous connective tissue disease mainly caused by structural mutations in type I collagen. Mutant collagen accumulates intracellularly, causing cellular stress that has recently been shown to be phenotype-related. Therefore, the aim of the study was to search for potential drugs reducing collagen accumulation and improving OI fibroblast homeostasis. We found that rosemary extract (RE), which is of great interest to researchers due to its high therapeutic potential, at concentrations of 50 and 100 µg/mL significantly reduced the level of accumulated collagen in the fibroblasts of four patients with severe and lethal OI. The decrease in collagen accumulation was associated with RE-induced autophagy as was evidenced by an increase in the LC3-II/LC3-I ratio, a decrease in p62, and co-localization of type I collagen with LC3-II and LAMP2A by confocal microscopy. The unfolded protein response, activated in three of the four tested cells, and the level of pro-apoptotic markers (Bax, CHOP and cleaved caspase 3) were attenuated by RE. In addition, the role of RE-modulated proteasome in the degradation of unfolded procollagen chains was investigated. This study provides new insight into the beneficial effects of RE that may have some implications in OI therapy targeting cellular stress.https://www.mdpi.com/1422-0067/23/18/10341rosemary extractcollagen type Iunfolded protein responseautophagyproteasomeskin fibroblasts |
| spellingShingle | Joanna Sutkowska-Skolimowska Justyna Brańska-Januszewska Jakub W. Strawa Halina Ostrowska Malwina Botor Katarzyna Gawron Anna Galicka Rosemary Extract-Induced Autophagy and Decrease in Accumulation of Collagen Type I in Osteogenesis Imperfecta Skin Fibroblasts International Journal of Molecular Sciences rosemary extract collagen type I unfolded protein response autophagy proteasome skin fibroblasts |
| title | Rosemary Extract-Induced Autophagy and Decrease in Accumulation of Collagen Type I in Osteogenesis Imperfecta Skin Fibroblasts |
| title_full | Rosemary Extract-Induced Autophagy and Decrease in Accumulation of Collagen Type I in Osteogenesis Imperfecta Skin Fibroblasts |
| title_fullStr | Rosemary Extract-Induced Autophagy and Decrease in Accumulation of Collagen Type I in Osteogenesis Imperfecta Skin Fibroblasts |
| title_full_unstemmed | Rosemary Extract-Induced Autophagy and Decrease in Accumulation of Collagen Type I in Osteogenesis Imperfecta Skin Fibroblasts |
| title_short | Rosemary Extract-Induced Autophagy and Decrease in Accumulation of Collagen Type I in Osteogenesis Imperfecta Skin Fibroblasts |
| title_sort | rosemary extract induced autophagy and decrease in accumulation of collagen type i in osteogenesis imperfecta skin fibroblasts |
| topic | rosemary extract collagen type I unfolded protein response autophagy proteasome skin fibroblasts |
| url | https://www.mdpi.com/1422-0067/23/18/10341 |
| work_keys_str_mv | AT joannasutkowskaskolimowska rosemaryextractinducedautophagyanddecreaseinaccumulationofcollagentypeiinosteogenesisimperfectaskinfibroblasts AT justynabranskajanuszewska rosemaryextractinducedautophagyanddecreaseinaccumulationofcollagentypeiinosteogenesisimperfectaskinfibroblasts AT jakubwstrawa rosemaryextractinducedautophagyanddecreaseinaccumulationofcollagentypeiinosteogenesisimperfectaskinfibroblasts AT halinaostrowska rosemaryextractinducedautophagyanddecreaseinaccumulationofcollagentypeiinosteogenesisimperfectaskinfibroblasts AT malwinabotor rosemaryextractinducedautophagyanddecreaseinaccumulationofcollagentypeiinosteogenesisimperfectaskinfibroblasts AT katarzynagawron rosemaryextractinducedautophagyanddecreaseinaccumulationofcollagentypeiinosteogenesisimperfectaskinfibroblasts AT annagalicka rosemaryextractinducedautophagyanddecreaseinaccumulationofcollagentypeiinosteogenesisimperfectaskinfibroblasts |