CELLULAR SIGNALLING
·
2025
·
IF 3.7
Xun Lu,Chengxin Ma,Dongxiao Li,Jianan Yang,Yuheng Sun,Bowen Liu,Binghai Zhao,Hongzhi Li
Hyperuricemia (HUA) is a prevalent metabolic disorder that contributes significantly to renal injury and may lead to the development of chronic kidney disease. Although previous studies have explored this condition, the molecular mechanisms underlying HUA-induced renal damage, particularly the role of small RNAs, remain inadequately understood. This study aimed to investigate the potential role of microRNA-93-5p (miR-93-5p) in HUA-associated renal injury. A comprehensive analysis was conducted to examine changes in miR-93-5p expression and its target gene, SMAD5, using knockout mouse models, cell cultures, transgenic techniques, and molecular biology methods. The findings demonstrated a significant upregulation of miR-93-5p in both HUA models and clinical serum samples, with a strong correlation to renal injury. Deletion of miR-93-5p resulted in increased SMAD5 expression and improved renal function, indicating that miR-93-5p contributed to renal injury by suppressing SMAD5 and promoting partial epithelial-mesenchymal transition in renal tubular epithelial cells. Transcriptomic analysis further revealed that miR-93-5p regulated numerous genes associated with inflammation, fibrosis, and apoptosis. Overall, these results underscore the pivotal role of miR-93-5p in HUA-induced renal damage through modulation of the SMAD5/Id2 signaling pathway, offering valuable insights into kidney disease pathophysiology and identifying potential therapeutic targets for clinical intervention.
研究领域:
分子生物学
·
肾脏病学
·
遗传学
·
细胞生物学
·
病理生理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
International Journal of Nanomedicine
·
2024
·
IF 6.6
Yi He,Lejia Zhang,Siyuan Huang,Yuquan Tang,Yiming Li,Hongyu Li,Guanhui Chen,Xun Chen,Xiliu Zhang,Wei Zhao,Feilong Deng,Dongsheng Yu
Background The ability of nanomaterials to induce osteogenic differentiation is limited, which seriously imped the repair of craniomaxillofacial bone defect. Magnetic graphene oxide (MGO) nanocomposites with the excellent physicochemical properties have great potential in bone tissue engineering. In this study, we aim to explore the craniomaxillofacial bone defect repairment effect of MGO nanocomposites and its underlying mechanism.Methods The biocompatibility of MGO nanocomposites was verified by CCK8, live/dead staining and cytoskeleton staining. The function of MGO nanocomposites induced osteogenic differentiation of BMSCs was investigated by ALP activity detection, mineralized nodules staining, detection of osteogenic genes and proteins, and immune-histochemical staining. BMSCs with or without MGO osteogenic differentiation induction were collected and subjected to high-throughput circular ribonucleic acids (circRNAs) sequencing, and then crucial circRNA circAars was screened and identified. Bioinformatics analysis, Dual-luciferase reporter assay, RNA binding protein immunoprecipitation (RIP), fluorescence in situ hybridization (FISH) and osteogenic-related examinations were used to further explore the ability of circAars to participate in MGO nanocomposites regulation of osteogenic differentiation of BMSCs and its potential mechanism. Furthermore, critical-sized calvarial defects were constructed and were performed to verify the osteogenic differentiation induction effects and its potential mechanism induced by MGO nanocomposites.Results We verify the good biocompatibility and osteogenic differentiation improvement effects of BMSCs mediated by MGO nanocomposites. Furthermore, a new circRNA-circAars, we find and identify, is obviously upregulated in BMSCs mediated by MGO nanocomposites. Silencing circAars could significantly decrease the osteogenic ability of MGO nanocomposites. The underlying mechanism involved circAars sponging miR-128-3p to regulate the expression of SMAD5, which played an important role in the repair craniomaxillofacial bone defects mediated by MGO nanocomposites.Conclusion We found that MGO nanocomposites regulated osteogenic differentiation of BMSCs via the circAars/miR-128-3p/SMAD5 pathway, which provided a feasible and effective strategy for the treatment of craniomaxillofacial bone defects.
研究领域:
生物材料
·
组织工程
·
骨再生
·
分子生物学
·
纳米技术
✓ 已验证
DOI
PubMed
高影响因子
International Journal of Nanomedicine
·
2024
·
IF 6.6
Min Chen,Tao Liu,Wenqiang Li,Yingting Li,Puxin Zhong,Huanchen Yan,Jingyin Kong,Weixiang Liang
Background Cartilage-related diseases, such as hypoplastic chondrodysplasia a rare genetic disorder that affects newborns, causing abnormal cartilage development and restricted skeletal growth. However, the development of effective treatment strategies for chondrodysplasia still faces significant challenges due to limitations in the controlled drug delivery, biocompatibility, and biodegradability of nanomedicines.Methods A biodegradable magnesium doped-silicon based-nanoplatforms based on silicon nanoparticles (MON) was constructed. Briefly, the MON was modified with sulfhydryl groups using MPTMS to form MOS. Further engineering of MOS was achieved by incorporating Mg2+ ions through the “dissolution-regrowth” method, resulting in MMOS. Ica was effectively loaded into the MMOS channels, and HA was anchored on the surface of MOS to obtain MMOS-Ica@HA nanoplatforms. Additionally, in vitro cell experiments and in vivo zebrafish embryo models were used to evaluate the effect of the nanoplatforms on cartilage differentiation or formation and the efficiency of treating chondrodysplasia.Results A series of characterization tests including TEM, SEM, DLS, XPS, EDX, and BET analysis validate the successful preparation of MOS-Ica@HA nanoplatforms. The prepared nanoplatforms show excellent dispersion and controllable drug release behavior. The cytotoxicity evaluation reveals the good biocompatibility of MOS-Ica@HA due to the sustained and controllable release of Ica. Importantly, the presence of Ica and Mg component in MOS-Ica@HA significantly promote chondrogenic differentiation of BMSCs via the Smad5/HIF-1α signaling pathway. In vitro and in vivo experiments confirmed that the nanoplatforms improved chondrodysplasia by promoting cartilage differentiation and formation.Conclusion The findings suggest the potential application of the developed biodegradable MMOS-Ica@HA nanoplatforms with acceptable drug loading capacity and controlled drug release in chondrodysplasia treatment, which indicates a promising approach for the treatment of chondrodysplasia.
研究领域:
生物医学工程
·
纳米技术
·
组织工程
·
再生医学
·
药学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Nature Communications
·
2023
·Vol. 14
·期 1
·1-18
·
IF 16.6
Li Zixin,He Danqing,Guo Bowen,Wang Zekun,Yu Huajie,Wang Yu,Jin Shanshan,Yu Min,Zhu Lisha,Chen Liyuan,Ding Chengye,Wu Xiaolan,Wu Tianhao,Gong Shiqiang,Mao Jing,Zhou Yanheng,Luo Dan,Liu Yan
Infected bone defects are a major challenge in orthopedic treatment. Native bone tissue possesses an endogenous electroactive interface that induces stem cell differentiation and inhibits bacterial adhesion and activity. However, traditional bone substitutes have difficulty in reconstructing the electrical environment of bone. In this study, we develop a self-promoted electroactive mineralized scaffold (sp-EMS) that generates weak currents via spontaneous electrochemical reactions to activate voltage-gated Ca 2+ channels, enhance adenosine triphosphate-induced actin remodeling, and ultimately achieve osteogenic differentiation of mesenchymal stem cells by activating the BMP2/Smad5 pathway. Furthermore, we show that the electroactive interface provided by the sp-EMS inhibits bacterial adhesion and activity via electrochemical products and concomitantly generated reactive oxygen species. We find that the osteogenic and antibacterial dual functions of the sp-EMS depend on its self-promoting electrical stimulation. We demonstrate that in vivo, the sp-EMS achieves complete or nearly complete in situ infected bone healing, from a rat calvarial defect model with single bacterial infection, to a rabbit open alveolar bone defect model and a beagle dog vertical bone defect model with the complex oral bacterial microenvironment. This translational study demonstrates that the electroactive bone graft presents a promising therapeutic platform for complex defect repair.
研究领域:
骨科
·
生物材料
·
组织工程
·
再生医学
·
生物医学工程
✓ 已验证
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）