Akademik Veri Yönetim Sistemi
TISSUE AND CELL, cilt.88, ss.1-9, 2024 (SCI-Expanded)
The effect of interleukin-38 (IL -38), a recently identified member of the IL -1 family with potential applications in various inflammation -related conditions, on ER stress has not been explored. Furthermore, its role in obesityassociated tendinopathy has not been investigated. In this study, human primary tenocytes were treated with palmitate (200 or 400 mu M) and palmitate plus IL -38 (0 -50 ng/mL) for 24 h. Western blotting was used to assess ER stress and tendinopathogenic markers in tenocytes. Monodansylcadaverine (MDC) staining was used to evaluate autophagosomes. Apoptosis was determined by cell viability assays, caspase 3 activity assays and TUNEL assays. Cell migration was evaluated by a cell scratch assay. Small interfering (si) RNA transfection was used for target gene silencing. Treatment of tenocytes with IL -38 attenuated apoptosis, restored the balance between MMPs and TIMP-1, and alleviated ER stress under palmitate conditions. IL -38 treatment enhanced AMPK phosphorylation and promoted the expression of autophagy markers related to LC3 conversion, p62 degradation, and autophagosome formation in cultured tenocytes. The effects of IL -38 on ER stress, apoptosis, and MMP-9, MMP-13, and TIMP-1 expression in palmitate-treated tenocytes were abrogated by AMPK siRNA or 3-methyladenine (3MA). These results suggest that IL -38 alleviates ER stress through the AMPK/autophagy pathway, thereby reducing apoptosis and preventing extracellular matrix (ECM) degradation in tenocytes under hyperlipidemic conditions. This study provides a promising therapeutic avenue for treating obesity -related tendinopathy using an endogenous compound such as IL -38.