Hydroxycamptothecin Prevents Fibrotic Pathways in Fibroblasts In Vitro.
Zhixiao YaoWei ZhengXiangqi ZhangHao XiongYun QianCunyi FanPublished in: IUBMB life (2019)
Peritendinous fibrosis, which leads to impaired tendon function, is a clinical problem worldwide, and it is urgent to explore potential ways to reduce the formation of peritendinous adhesion. Several studies have demonstrated the biological roles of hydroxycamptothecin (HCPT) in inhibiting fibrosis in different tissues. In this study, we investigated whether HCPT could inhibit tendon fibrosis in vitro. Our results revealed that HCPT inhibited transforming growth factor (TGF)-β1-induced cell viability of human fibroblasts, decreased excessive cell hyperproliferation and promoted fibroblasts apoptosis. In addition, HCPT treatment also inhibited expression of fibrosis genes COL3A1 and α-smooth muscle actin (α-SMA). In terms of mechanism, we pretreated fibroblasts with the endoplasmic reticulum stress (ER) inhibitor salubrinal and RNA-dependent protein kinase-like ER kinase (PERK) short hairpin RNA, these treatments abolished the inhibitory effects of HCPT on fibrosis, thereby suggesting that HCPT's inhibition of TGF-β1-induced tendon fibrosis might be mediated by the PERK signaling pathway in vitro. In conclusion, our results suggested that HCPT had protective effects on peritendinous tissue fibrosis and might be promising in future clinical applications. © 2019 IUBMB Life, 71(5):653-662, 2019.
Keyphrases
- endoplasmic reticulum stress
- transforming growth factor
- signaling pathway
- induced apoptosis
- epithelial mesenchymal transition
- smooth muscle
- protein kinase
- endoplasmic reticulum
- extracellular matrix
- gene expression
- diabetic rats
- bone marrow
- risk assessment
- cell proliferation
- anterior cruciate ligament reconstruction
- escherichia coli
- high glucose
- staphylococcus aureus
- systemic sclerosis
- pi k akt
- cell therapy
- drug induced
- dna methylation
- physical activity
- mouse model
- nucleic acid
- combination therapy
- rotator cuff
- weight gain
- pluripotent stem cells
- biofilm formation
- stress induced
- human health