ABSTRACT
Epithelial-mesenchymal transition (EMT), known as the transition of tubular epithelial cells into fibroblasts, is one of the potential mechanisms of renal fibrosis, which promotes the development of diabetic kidney disease (DKD). Etoposide-induced protein 2.4 (EI24) is known as an endoplasmic reticulum (ER)-localized Bcl-2-binding transmembrane protein with various functions that can affect autophagy, apoptosis and differentiation. However, whether EI24 is involved in EMT of renal tubular epithelial cells and the exact mechanism is still not known. In this study, we first reported that EI24 expression was significantly downregulated in the kidneys of diabetic mice and in high glucose-stimulated HK2 cells. Knockdown of EI24 led to EMT of HK2 cells, as indicated by decreased E-cadherin and increased α-smooth muscle actin (α-SMA). Meanwhile, overexpression of EI24 ameliorated high glucose-induced EMT of HK2 cells via activation of the adenosine monophosphate-activated protein kinase (AMPK) pathway. Then, DNA methyltransferase (DNMT) inhibitor 5-Aza-2'-deoxycytidine (5-Aza) treatment enhanced EI24 expression and alleviated EMT in high glucose-treated HK2 cells and the kidneys of diabetic mice. Furthermore, DNMT1 and DNMT3a upregulation were found to be involved in the decrease of EI24 in high glucose-stimulated HK2 cells. Silencing of DNMT1 and DNMT3a effectively reversed high glucose-induced downregulation of EI24 and aggravation of EMT. Our findings demonstrate that the DNA methyltransferase-regulated EI24 affects EMT of renal tubular cells via AMPK signaling pathway. It is suggested that EI24 may be a potential therapeutic target for diabetic renal injury.
Subject(s)
Epithelial-Mesenchymal TransitionABSTRACT
Osteoarthritis (OA) is a common disease of the elderly, posing a major personal and socioeconomic burden. OA is characterized by painful degeneration of articular cartilage, and its prevention, diagnosis and treatment remain problematic. Circular RNAs (circRNAs) constitute a large family of non-coding RNAs that are widely distributed, stable, conserved and tissue-specific. circRNAs have been found to be closely associated with OA development and progression, and they may serve as targets for disease prevention and treatment. The aim of the present article was to review the roles of circRNAs in OA and discuss possible treatment strategies.
ABSTRACT
In the process of repairing of bone defects, bone scaffold materials need to be implanted to restore the corresponding tissue structure at the injury. At present, the repair materials used for bone defects mainly include autogenous bone, allogeneic bone, metal materials, bioceramics, polymer materials and various composite materials. Different materials have demonstrated strong reconstruction ability in bone repair, but the ideal bone implants in the clinic are still yet to be established. Except for autogenous bone, other materials used in bone defect repair are unable to perfectly balance biocompatibility, bone formation, bone conduction and osteoinduction. Combining the latest advances in materials sciences and clinical application, we believe that composite materials supplementedwith Chinese medicine, tissue cells, cytokines, trace elements, etc. and manufactured using advanced technologies such as additive manufacturing technology may have ideal bone repair performance, and may have profound significance in clinical repair of bone defects of special type. This article reviewed to the domestic and foreign literature in recent years, and elaborates the current status of bone defect repair materials in clinical application and basic research in regard to the advantages, clinical options, shortcomings, and how to improve the autogenous bone, allogeneic bone and artificial bone materials, in order to provide a theoretical basis for clinical management of bone defects.
