Rosemary Extract-Induced Autophagy and Decrease in Accumulation of Collagen Type I in Osteogenesis Imperfecta Skin Fibroblasts.
Joanna SutkowskaJustyna Brańska-JanuszewskaJakub Wladyslaw StrawaHalina OstrowskaMalwina BotorKatarzyna GawronAnna GalickaPublished in: International journal of molecular sciences (2022)
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.
Keyphrases
- wound healing
- cell death
- induced apoptosis
- endoplasmic reticulum stress
- tissue engineering
- oxidative stress
- signaling pathway
- drug induced
- diabetic rats
- high glucose
- mass spectrometry
- cell cycle arrest
- high resolution
- stem cells
- risk assessment
- endothelial cells
- type iii
- cancer therapy
- solid phase extraction
- human health
- protein protein