Frontiers in Medicine
·
2024
·
IF 3.1
Liu Yan,Ge Ri-Li,Shan Zhen-Zhen,Wang Yan-Jun,Yang Yan-Yan,Sun Xue,Luo Peng-Li
Podocytopathies encompass kidney diseases where direct or indirect podocyte injury leads to proteinuria or nephrotic syndrome. Although Semaphorin3A (Sema3A) is expressed in podocytes and tubular cells in adult mammalian kidneys and has a common effect on the progression of podocyte injury, its mechanism remains unclear. Previous studies have shown increased Sema3A expression in various glomerulopathies, indicating a gap in understanding its role. In this study, analysis of human data revealed a positive correlation between the levels of urinary Sema3A and Podocalyxin (PCX), suggesting a close relationship between Sema3A and podocyte loss. Furthermore, the impact of Adriamycin on podocytes was investigated. Adriamycin induced podocyte migration and apoptosis, along with an increase in Sema3A expression, all of which were ameliorated by the inhibition of Sema3A. Importantly, TRPC5 was found to increase the overexpression of Sema3A in podocytes. A TRPC5 inhibitor, AC1903, alleviated podocyte migration and apoptosis, inhibiting the formation of lamellar pseudopodia in the podocyte cytoskeleton by lowering the expression of Rac1. Furthermore, AC1903 relieved massive albuminuria and foot process effacement in the kidneys of Adriamycin-treated mice in vivo. In conclusion, our findings suggest that Sema3A may impact the cytoskeletal stability of podocytes through TRPC5 ion channels, mediated by Rac1, ultimately leading to foot process effacement. Notably, AC1903 demonstrates the potential to reverse Adriamycin-induced foot process fusion and urine protein. These results contribute to a deeper understanding of the mechanisms involved in podocytopathies and highlight the therapeutic potential of targeting the Sema3A-TRPC5 pathway.
研究领域:
肾脏病学
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分子生物学
✓ 已验证
DOI
PubMed
高影响因子
METABOLIC BRAIN DISEASE
·
2021
·Vol. 36
·期 7
·2059-2069
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IF 3.584
Yang Ling,Wang Lijuan,Wang Juan,Liu Ping
Long non-coding RNAs (lncRNAs) play important roles in ischaemic stroke. This study aimed to investigate the role and potential mechanism of lncRNA Gm11974 in ischaemic stroke. Mouse neuroblastoma N2a cells were treated with oxygen–glucose deprivation (OGD). The levels of Gm11974, microRNA-122-5p (miR-122-5p) and semaphorin 3A (SEMA3A) were detected by quantitative real-time PCR (qRT-PCR) or western blot. Cell viability and apoptosis were determined by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) assay, Caspase-3 Assay Kit and flow Cytometry. The levels of oxidative stress indicators were measured by using commercial kits. The relationship between miR-122-5p and Gm11974 or SEMA3A was verified by dual-luciferase reporter, RNA immunoprecipitation and RNA pull-down assays. Middle cerebral artery occlusion (MCAO) in mice was used to mimic ischaemic stroke. Gm11974 and SEMA3A were up-regulated, while miR-122-5p was down-regulated in OGD-treated N2a cells and MCAO mice. Down-regulation of Gm11974 ameliorated OGD-mediated N2a cell damage by increasing cell viability and reducing cell apoptosis and oxidative stress. Gm11974 promoted OGD-induced injury in N2a cells via negatively regulating miR-122-5p. Also, miR-122-5p alleviated OGD-resulted N2a cell injury by targeting SEMA3A. Moreover, silencing of Gm11974 decreased infarct volume and neurological score in MCAO mice. Knockdown of Gm11974 attenuated neuronal injury in ischaemic stroke by regulating miR-122-5p/SEMA3A signaling pathway.
研究领域:
神经科学
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分子生物学
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细胞生物学
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病理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CHEMICAL ENGINEERING JOURNAL
·
2023
·
IF 15.1
Fancheng Xu,Tian Deng,Wenfeng Li,Yufeng Ai,Jianxin Wu,Yuting Yang,Chenjiang He,Kaiqiang Yang,Li Li,Fang Dai,Li Song
Periodontitis is a pathological disorder characterized by inflammation and tissue destruction; it is primarily attributed to bacterial infection and immune responses. Nevertheless, existing strategies for drug delivery in periodontal treatment are insufficient to accommodate the intricate anatomical morphology of the periodontium and the complex oral environment. Furthermore, the disordered release of antibacterial agents and bone-promoting substances are not conducive to the natural healing of periodontal tissues, thus resulting in suboptimal therapeutic outcomes for periodontitis. In this study, we successfully co-loaded methylene blue (MB) and poly(lactic-co-glycolic acid) microspheres encapsulating Sema3A into a dopamine-grafted sodium alginate hydrogel (SA-DA). Experimental evidence indicates that MB/Sema3A@SA-DA exhibits favorable injectability, adhesion, and compression resistance characteristics, thus allowing it to adapt to the intricate therapeutic conditions of the oral cavity. The prompt release of MB (within 14 h) demonstrates its high antibacterial efficacy against periodontal pathogens upon exposure to 660 nm light, thereby establishing a microenvironment conducive to osteogenesis devoid of bacterial interference. Furthermore, the protracted release of Sema3A (within 28 d) shows noteworthy osteogenic capabilities and facilitates the polarization of macrophages toward the M2 phenotype. In a rat model of periodontitis, MB/Sema3A@SA-DA can be perfectly applied in situ to local periodontal lesions, and the sequential release of MB and Sema3A effectively achieved antibacterial, anti-inflammatory, and osteogenic effects. This therapeutic system avoids the abuse of antibiotics, surgical trauma, and repetitive administration. Hence, MB/Sema3A@SA-DA emerges as a safe, effective, minimally invasive, comfortable, and cost-effective treatment strategy with considerable potential for clinical implementation in periodontitis management.
研究领域:
口腔科学
·
药剂学
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生物医学工程
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材料科学
✓ 已验证
DOI
高影响因子
危险品化学品经营许可证（带存储）