EUROPEAN JOURNAL OF PHARMACOLOGY
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2024
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IF 4.2
Congna Zi,Xian Ma,Maodong Zheng,Ying Zhu
Myocardial injury triggers intense inflammatory reactions and oxidative stress responses. S100 calcium-binding protein A16 (S100A16), a multi-functional calcium (Ca 2+ )-binding protein, participates in inflammatory responses and contributes to ischemia/reperfusion (I/R) injury. Nevertheless, the precise mechanism by which S100A16 operates in myocardial I/R injury remains uncertain. Cardiac I/R injury was produced by ligation/release of the left anterior descending artery, and mouse cardiac cells were subjected to hypoxia/reoxygenation (H/R) to determine the biological effects in vitro . We demonstrated that S100A16 was upregulated in the ischemic hearts and cardiac cells after I/R and H/R injury. Adenovirus-mediated S100A16 inhibition led to a considerable improvement in cardiac function with a reduced infarct size, accompanied by a reduction in cardiomyocyte apoptosis. Similar effects of S100A16 inhibition on inflammation and reactive oxygen species (ROS) production were observed in cultured cardiomyocytes. Importantly, we showed that I/R and H/R treatment upregulated the expression of voltage-dependent anion channel 1 (VDAC1), which subsequently activated NF-κB/p65 to facilitate the binding of NF-κB/p65 to the S100A16 promoter, thereby activating the transcription and expression of S100A16. Mechanically, S100A16 responded to increasing Ca 2+ and interacted with calmodulin (CaM) to regulate the activation of calcium/calmodulin-dependent protein kinase 2 (CAMKK2)/AMPK pathway. In conclusion, VDAC1 sustained the NF-κB p65 pathway activation to elicit increased S100A16 expression, contributing to myocardial damage and heart failure post-I/R via the CaM/CaMKK2/AMPK pathway. This study revealed a crucial role of the VDAC1-S100A16 axis in the process of myocardial I/R injury, providing novel molecular targets for the treatment of cardiac conditions associated with I/R injury.
研究领域:
心脏病学
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分子生物学
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细胞生物学
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病理生理学
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产品关联
DOI
PubMed
高影响因子
BIOCHEMICAL ENGINEERING JOURNAL
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2023
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IF 3.9
Yi Zhou,Yawen Chen,Yuanyuan Zhao,Qiaohui Lu,Shihao Li,Wen-song Tan,Yan Zhou
Hydrostatic pressure (HP) is one of the important mechanical stimuli to maintain the structure and function of bone tissue. Under non-physiological conditions, abnormal increases or decreases in HP can lead to loss of bone tissue function. Although HP has been proven to affect osteogenic differentiation, the rules and mechanisms of its regulatory effect are still unclear. In this study, the HP showed a marginal effect on promoting osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs). The regulation of osteogenic differentiation by HP is closely related to the Piezo1 ion channel. On the one hand, the activity of mTOR is inhibited by HP through the CaMKK2/AMPKα/mTOR signaling axis, thereby promoting the osteogenic differentiation. On the other hand, the cell morphology is also regulated by HP and tends to be round, which is not conducive to osteogenesis. The two regulatory modes jointly control the ultimate osteogenic differentiation ability of BMSCs in a complex way. This study provides new insights into the mechanism by which HP regulates osteogenic differentiation, suggesting the need to consider the role of signaling cascades and physical changes simultaneously.
研究领域:
生物力学
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干细胞生物学
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骨组织工程
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DOI
高影响因子
KAOHSIUNG JOURNAL OF MEDICAL SCIENCES
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2025
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IF 3.1
Yan-Jun Yang,Jiu-Sheng Li
Sacubitril/valsartan (Sac/Val) has emerged as an effective compound with myocardium-protective functions in experimental and clinical trials for heart failure. This study investigated the function of Sac/Val in hypertensive heart disease (HHD) and explored the underlying mechanism. Spontaneous hypertensive rats (SHRs) were used as an animal model of HHD. Sac/Val administration ameliorated pathological injury, fibrosis, cell apoptosis, inflammatory cytokine production, and oxidative stress in the myocardial tissues of HHD rats. Similar findings were observed in vitro, where Sac/Val treatment reduced inflammation, oxidative stress, and fibrosis-related markers in Ang II-challenged H9C2 cells. Calcium/calmodulin-dependent protein kinase kinase 2 (CAMKK2) was identified as a target of Sac/Val which was downregulated in HHD models, and CAMKK2 protein levels were restored by Sac/Val treatment. Lentiviral vector-induced CAMKK2 knockdown reduced the phosphorylation levels of AMPKα, AKT, and GSK-3β, thereby negating the treatment effects of Sac/Val. Further treatment with AICAR, an AMPK agonist, significantly reactivated the AMPK/AKT/GSK-3β cascade and alleviated inflammatory injury in both models. Collectively, this study suggests that Sac/Val ameliorates inflammation and oxidative stress in HHD by restoring the CAMKK2 protein and activating the AMPK/AKT/GSK-3β cascade.
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产品关联
DOI
PubMed
高影响因子
ADVANCED FUNCTIONAL MATERIALS
·
2024
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IF 18.5
Yizhou Zhu,Chaofeng Wang,Can Ai,Yiming Xiang,Congyang Mao,Wei Qiao,Jun Wu,John Akrofi Kubi,Xiangmei Liu,Shuilin Wu,Xin Zhao,Bin Li,Kelvin W. K. Yeung
Early osteoimmune microenvironment disorder at the interface between bone and implant can lead to implant loosening, which prolongs patient convalescence, exacerbates postoperative complications, and potentially results in implant failure. The timely regulation of macrophages primarily orchestrates the entire long-term regeneration process. Here, it is proposed to precisely direct macrophage polarization using localized photoelectrical signals generated by an excitable surface in response to remote stimulation via near-infrared light (NIR). The photocurrent generated from the n–n heterojunction between calcium titanate (CaTiO 3 ) and defective titanium dioxide (TiO 2 -V o ) on the excitable surface can accurately direct macrophage polarization, suppressing acute inflammation at the early stage of post-implantation and establishing a favorable osteoimmune microenvironment that promotes bone-to-implant integration. Mechanistic study reveals that photoelectric signals initiate increased calcium influx via voltage-gated calcium ion channels, subsequently modulating calcium/calmodulin-dependent protein kinase kinase 2 (Camkk2) and calcium/calmodulin-dependent protein kinase I (Camk1) expression to regulate macrophage polarization. This optimization of the osteoimmune microenvironment results in enhanced mesenchymal stem cells (MSCs) recruitment and osteogenesis, ultimately accelerating bone-to-implant integration within 14 days post-implantation. This research presents a novel method for adjusting in vivo spatiotemporal immune responses through the use of noninvasive and externally-controlled targeted stimulations.
研究领域:
生物医学工程
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免疫学
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组织工程
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材料科学
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产品关联
DOI
高影响因子
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