ACS Applied Materials & Interfaces
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2025
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IF 8.2
Longwu Xu,Lin Ma,Xiufeng Xu,Yifan Wang,Qiuhong Jiao,Shulan Pang,Yuying Wang,Weiwei Yang,Shuai Mao,Yudan Zhao,Jie Hao,Tao Huang,Peikang Dong,Yingshuai Wang,Tao Wang
Aortic dissection (AD) is a life-threatening condition with a high mortality rate. Oxidative stress and endothelial and vascular smooth muscle cell migration contribute to AD pathogenesis. Herein, we investigated the therapeutic potential of hydrogen (H2), delivered via magnesium diboride nanosheets (MBNs), in a murine model of β-aminopropionitrile-induced AD. This treatment significantly improved survival rate and reduced AD progression, as evidenced by improved aortic wall structure and reduced false lumen formation. Transcriptomic analysis indicated modulation of the RhoA/ROCK pathway, confirmed using Western blotting, immunohistochemistry, and immunofluorescence, which showed significant downregulation of RhoA and ROCK2 after 28 days of treatment (P < 0.05). These findings suggest that hydrogen released from MBNs attenuates AD progression through reactive oxygen species scavenging and RhoA/ROCK pathway inhibition.
研究领域:
医学
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分子生物学
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DOI
PubMed
高影响因子
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
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2024
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IF 5.7
Chenjiao Miao,Zuoyao Wu,Yafei Sun,Zheng Cao
Deoxynivalenol (DON) poses a serious global food safety risk due to its high toxicity and contamination rate. It disrupts the intestinal epithelial barrier, allowing exogenous toxins to enter the circulation and resulting in sepsis and systemic toxicity. In this research, 32 male Kunming mice and Porcine Small Intestinal Epithelial (IPEC-J2) cells were treated with DON at 0–4.8 mg/kg (7 d) and 0–12 μM (24 h), respectively. Histopathological results revealed that DON disrupted the intestinal epithelial barrier, causing apoptosis and tight junction (TJ) injury. Immunofluorescence and protein expression results showed that DON-induced p53-dependent mitochondrial pathway apoptosis and fibrillar actin (F-actin)-associated TJ injury and that the RhoA/ROCK pathway were activated in mice jejunal tissue and IPEC-J2 cells. Pretreatment with RhoA or ROCK inhibitors (Rosin or Y-27632) maintained DON-induced apoptosis and F-actin-associated TJ injury in IPEC-J2 cells. Thus, DON induces damage to the intestinal epithelial barrier through the RhoA/ROCK pathway-mediated apoptosis and F-actin-associated TJ disruption.
CAS / MDL:
研究领域:
毒理学
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细胞生物学
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食品科学
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PubMed
高影响因子
FITOTERAPIA
·
2025
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IF 2.6
Xuan Zhang,Jie Weng,Yi Luo,Hongcun Liu,Jing Yan,Zhiqiang Gong,Chaonan Kong,Xue Li,Lifang Yang,Mingguo Jiang
To elucidate the efficacy and potential molecular mechanisms underlying the therapeutic effects of Spatholobi Caulis flavonoids (SCF) in the treatment of primary dysmenorrhea (PD). The present study established oxytocin-induced uterine contractions in vitro and a model of PD in rats evoked by estradiol benzoate and oxytocin. The uterine contraction experiments demonstrated that SCF significantly inhibited uterine smooth muscle tone by 62.07 %. SCF effectively attenuated the torsional response in PD rats, normalised the PGF2α/PGE2 ratio, and reduced NO and Ca 2+ levels. The constituents of SCF were evaluated by using a Liquid Chromatograph Mass Spectrometer(LC-MS) method, and 11 flavonoid components were preliminarily deduced. Network pharmacology and molecular docking (MD) techniques were used to predict therapeutic targets, with the former suggesting key targets such as RhoA, VEGFA, and PIK3CA, while the latter indicated that 10 compounds had a strong binding affinity for RhoA. The expression of CALM, RhoA, ROCK1, PIK3CA, and AKT was down-regulated at both the protein and mRNA levels. Additionally, the expression levels of genes associated with VEGFA, IP3R, MLCK and NOS3 were found to be regulated. The collective evidence from this study suggests that SCF may attenuate uterine spasm by inhibiting the RhoA/ROCK signaling pathway, decreasing the levels of PGF2α, NO and Ca 2+ , and increasing the content of PGE2. This study provides a theoretical basis for the application of SCF in the treatment of PD.
研究领域:
药理学
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分子生物学
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DOI
PubMed
高影响因子
Animal Models and Experimental Medicine
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2024
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IF 3.8
Ce Zhang,Jia Zheng,Xueping Yu,Binglin Kuang,Xiaohong Dai,Lei Zheng,Weiwei Yu,Wei Teng,Hongtao Cao,Mingyue Li,Jiayong Yao,Xiaoying Liu,Wei Zou
Background Blocking the RhoA/ROCK II/MLC 2 (Ras homolog gene family member A/Rho kinase II/myosin light chain 2) signaling pathway can initiate neuroprotective mechanisms against neurological diseases such as stroke, cerebral ischemia, and subarachnoid hemorrhage. Nevertheless, it is not clear whether and how disrupting the RhoA/ROCK II/MLC 2 signaling pathway changes the pathogenic processes of the blood–brain barrier (BBB) after intracerebral hemorrhage (ICH). The present investigation included the injection of rat caudal vein blood into the basal ganglia area to replicate the pathophysiological conditions caused by ICH. Methods Scalp acupuncture (SA) therapy was performed on rats with ICH at the acupuncture point “Baihui”-penetrating “Qubin,” and the ROCK selective inhibitor fasudil was used as a positive control to evaluate the inhibitory effect of acupuncture on the RhoA/ROCK II/MLC 2 signaling pathway. Post-assessments included neurological deficits, brain edema, Evans blue extravasation, Western blot, quantitative polymerase chain reaction, and transmission electron microscope imaging. Results We found that ROCK II acts as a promoter of the RhoA/ROCK II/MLC 2 signaling pathway, and its expression increased at 6 h after ICH, peaked at 3 days, and then decreased at 7 days after ICH, but was still higher than the pre-intervention level. According to some experimental results, although 3 days is the peak, 7 days is the best time point for acupuncture treatment. Starting from 6 h after ICH, the neurovascular structure and endothelial cell morphology around the hematoma began to change. Based on the changes in the promoter ROCK II, a 7-day time point was selected as the breakthrough point for treating ICH model rats in the main experiment. The results of this experiment showed that both SA at “Baihui”-penetrating “Qubin” and treatment with fasudil could improve the expression of endothelial-related proteins by inhibiting the RhoA/ROCK II/MLC 2 signaling pathway and reduce neurological dysfunction, brain edema, and BBB permeability in rats. Conclusion This study found that these experimental data indicated that SA at “Baihui”-penetrating “Qubin” could preserve BBB integrity and neurological function recovery after ICH by inhibiting RhoA/ROCK II/MLC 2 signaling pathway activation and by regulating endothelial cell–related proteins.
研究领域:
神经科学
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中医学
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分子生物学
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DOI
PubMed
高影响因子
TOXICOLOGY AND APPLIED PHARMACOLOGY
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2019
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IF 3.585
Xue-Ying Wang,Dan Mo,Wen Tian,Xiao-Xiao Liu,Ya-Guang Zhou,Yang Sun,Ying-Da Feng,Xiong Xiao,Xiao-Wei Hao,Hui-Nan Zhang,Chen Li,Wei Cao,Xiao-Qiang Li
Hypoxic pulmonary vasoconstriction (HPV) can be modulated by Rho/Rho kinase signaling, which can alter HPV vascular function via regulating myosin light chain phosphorylation, in a manner generally believed to be Ca 2+ -independent. We hypothesized that the RhoA/ROCK signaling pathway also can regulate HPV vascular function via a Ca 2+ -dependent mechanism, signaling through the functional transient receptor potential canonical (TRPC) channels. In this study, male BALB/c mice were exposed to normoxic or 10% oxygen (hypoxic) conditions for six weeks, after which systolic pressure and right ventricular hypertrophy were assessed. Transient intracellular calcium was monitored using a fluorescence imaging system. Muscle tension was measured with a contractile force recording system, and protein expression was assessed by immunoblotting . We found that the expressions of RhoA and ROCK were increased in mouse pulmonary arteries (PAs) under conditions of chronic hypoxia . Inhibition of the RhoA/ROCK signaling pathway prevented the development of hypoxic pulmonary hypertension (HPH), as evidenced by significantly reduced PA remodeling and pulmonary vasoconstriction. Immunoblotting results revealed that inhibition of the RhoA/ROCK signaling pathway significantly decreased the expression of HIF-1α. Knockdown of HIF-1α down-regulated the expression and function of the TRPC1 and TRPC6 channels in PASMCs under conditions of hypoxia. Contraction of the PAs and a Ca 2+ influx into PASMCs through either receptor- or store-operated Ca 2+ channels were also increased after hypoxia. However, RhoA/ROCK inhibitors markedly attenuated these changes. These results indicate that inhibition of the RhoA/ROCK signaling pathway ameliorates HPH via HIF-1α-dependent functional TRPCs.
研究领域:
心血管生理学
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分子生物学
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药理学
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PubMed
高影响因子
Journal of Pharmaceutical Analysis
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2024
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IF 6.1
Xuedan Han,Jialei Liu,Yidong Zhang,Eric Tse,Qiyi Yu,Yu Lu,Yi Ma,Lufeng Zheng
Anlotinib has strong antiangiogenic effects and leads to vessel normalization. However, the "window period" characteristic in regulating vessel normalization by anlotinib cannot fully explain the long-term survival benefits achieved through combining it with other drugs. In this study, through RNA sequencing and label-free quantitative proteomics analysis, we discovered that anlotinib regulated the expression of components of the extracellular matrix (ECM), leading to a significant reduction in ECM stiffness. Our bioinformatic analysis revealed a potential positive relationship between the ECM pathway and gefitinib resistance, poor treatment outcomes for programmed death 1 (PD-1) targeting, and unfavourable prognosis following chemotherapy in lung cancer patients. We administered anlotinib in combination with these antitumour drugs and visualized their distribution using fluorescent labelling in various tumour types. Notably, our results demonstrated that anlotinib prolonged the retention time and distribution of antitumour drugs at the tumour site. Moreover, the combination therapy induced notable loosening of the tumour tissue structure. This reduction was associated with decreased interstitial fluid pressure and tumour solid pressure. Additionally, we observed that anlotinib effectively suppressed the RhoA/ROCK signalling pathway. These findings suggest that, in addition to its antiangiogenic and vessel normalization effects, anlotinib can increase the distribution and retention of antitumour drugs in tumours by modulating ECM expression and physical properties through the RhoA/ROCK signalling pathway. These valuable insights contribute to the development of combination therapies aimed at improving tumour targeting in cancer treatment.
研究领域:
肿瘤学
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药理学
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癌症生物学
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分子生物学
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DOI
PubMed
高影响因子
JOURNAL OF THROMBOSIS AND THROMBOLYSIS
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2024
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IF 2.3
He Chengjian,Song Xiaojing,Zhu Zigui,Xiao Yan,Chen Jiacheng,Yao Hongyi,Xie Rongjun
Ghrelin exerts widespread effects in several diseases, but its role and mechanism in Acute Traumatic Coagulopathy (ATC) are largely unknown. The effect of ghrelin on cell proliferation was examined using three assays: 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT), Lactate Dehydrogenase (LDH), and flow cytometry. The barrier function of the endothelial cells was evaluated using the Trans-Endothelial Electrical Resistance (TEER) and the endothelial permeability assay. An ATC mouse model was established to evaluate the in vivo effects of ghrelin. The Ras homolog family member A (RhoA) overexpression plasmid or adenovirus was used to examine the molecular mechanism of ghrelin. Ghrelin enhanced Human Umbilical Vein Endothelial Cells (HUVEC) proliferation and endothelial cell barrier function and inhibited HUVEC permeability damage in vitro. Additionally, ghrelin decreased the activated Partial Thromboplastin Time (aPTT) and Prothrombin Time (PT) in mice blood samples in the ATC mouse model. Ghrelin also improved the pathological alterations in postcava. Mechanistically, ghrelin acts through the RhoA/ Rho-associated Coiled-coil Containing Kinases (ROCK)/ Myosin Light Chain 2 (MLC2) pathway. Furthermore, the protective effects of ghrelin, both in vitro and in vivo, were reversed by RhoA overexpression. Our findings demonstrate that ghrelin may reduce vascular endothelial cell damage and endothelial barrier dysfunction by blocking the RhoA pathway, suggesting that ghrelin may serve as a potential therapeutic target for ATC treatment. Graphical Abstract We explored the effects of ghrelin on coagulopathy and vascular endothelial injury in vivo by establishing an ATC mouse model, and investigated the effects of ghrelin on LPS-induced HUVECs cell damage in vitro. The RhoA overexpression plasmid or adenovirus was used to examine the molecular mechanism. Abbreviations : ATC =acute traumatic coagulopathy; HUVECs =Human Umbilical Vein Endothelial Cells; LPS =lipopolysaccharide; RhoA =The Ras homolog family member A; aPTT =activated partial thromboplastin time; PT =prothrombin time; TEER =trans-endothelial electrical resistance
研究领域:
血液学
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血管生物学
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药理学
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分子生物学
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DOI
PubMed
高影响因子
MOLECULAR PSYCHIATRY
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2026
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IF 10.4
Liao Kang,Xie Meng,Ibáñez Carlos F.
Therapeutic development in Alzheimer’s Disease (AD) has for the most part been focused on reducing β-amyloid load. Nevertheless, neurofibrillary tangles (NFTs), produced by aggregation of hyper-phosphorylated Tau protein, correlate with neurodegeneration and cognitive impairment significantly better than amyloid accumulation in AD patients. Here we report that P301S mice, a model of Tau-mediated neurodegeneration, carrying mutant variants of the p75 neurotrophin receptor (p75 NTR ) deficient in RhoA/ROCK signaling are protected from neurodegeneration and cognitive impairment. Both p75 ∆DD , lacking the death domain, and triple mutant p75 KKEA , unable to interact with RhoGDI, decreased insoluble Tau species, reduced gliosis, neurodegeneration and synapse loss, and improved spatial learning and memory in P301S mice. Intriguingly, p75 C259A , a variant unresponsive to neurotrophins but still competent for RhoA signaling induced by myelin-derived ligands, did not afford any neuroprotection. P301S neurons expressing p75 ∆DD or p75 KKEA , but not p75 C259A , showed reduced phospho-Tau and ROCK and GSK3β activity, the two main kinases responsible for Tau phosphorylation. In line with this, treatment with myelin-associated glycoprotein (MAG) enhanced Tau phosphorylation and ROCK activity in P301S neurons expressing wild type p75 NTR or p75 C259A , but not p75 ∆DD or p75 KKEA . Together, these results indicate that p75 NTR contributes to AD Tauopathy by enhancing the activity of the RhoA-ROCK pathway.
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高影响因子
Advanced Healthcare Materials
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2023
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IF 10
Dengjie Yu,Qingbin Nie,Jiangtao Xue,Ruizeng Luo,Shiwang Xie,Shengyu Chao,Engui Wang,Linlin Xu,Yizhu Shan,Zhuo Liu,Yusheng Li,Zhou Li
Osteoarthritis (OA) is the most prevalent joint degenerative disease characterized by chronic joint inflammation. The pathogenesis of OA has not been fully elucidated yet. Cartilage erosion is the most significant pathological feature in OA, which is considered as the result of the cytomechanical homeostasis destruction. The cytomechanical homeostasis is maintained by the dynamic interaction between cells and the extracellular matrix, which can be reflected by cell traction force (CTF). It is critical to assess the CTF for providing a deeper understanding of the cytomechanical homeostasis destruction and progression in OA. In this study, a silicon nanopillar array (Si-NP) with high spatial resolution and aspect ratio is fabricated to investigate the CTF in response to OA. We discover the CTF is degraded in OA, which is attributed to the F-actin reorganization induced by the activation of RhoA/ROCK signaling pathway. Si-NP also show promising potential as a mechanopharmacological assessment platform for OA drug screening and evaluation. This article is protected by copyright. All rights reserved
研究领域:
骨科
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生物力学
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纳米技术
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药理学
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DOI
PubMed
高影响因子
CANCER LETTERS
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2026
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IF 11.8
Jie Wang,Huihao Ma,Baozhi Feng,Yan Fu,Chunlin Lu,Mingyang Fei,Yuxin Zhang,Bin Dong,Ying Li,Jing Liu
Aldo-keto reductase family 1 member C3 (AKR1C3) is a pivotal metabolic enzyme involved in arachidonic acid (AA) metabolism and cancer metabolic reprogramming, which plays a critical role in the initiation and progression of glioblastoma (GBM). We integrated single-cell and transcriptome data to characterize AA metabolism features in GBM and identify the key gene AKR1C3. Using CCK8 assays, wound-healing assays, transwell assays, and mouse tumor formation experiments, we elucidated the effects of AKR1C3. Dual-luciferase reporter assays and ChIP-PCR experiments were performed to investigate the regulation of transcription factor JUN on AKR1C3 expression. RNA-seq analysis, combined with rescue experiments, demonstrated that AKR1C3 significantly regulates the RhoA/ROCK pathway. Arachidonic acid metabolism is closely associated with clinical outcomes in glioma, with AKR1C3 identified as a key gene within this pathway. AKR1C3 knockdown enhanced tumor cell proliferation, migration, and invasion, whereas AKR1C3 overexpression suppressed these malignant behaviors. In vivo experiments further confirmed the inhibitory effect of AKR1C3 on glioma progression. Dual-luciferase reporter and ChIP-PCR assays demonstrated that JUN acts as an upstream regulator of AKR1C3. ELISA results indicated that AKR1C3 overexpression reduced cellular PGD2 levels. RNA-seq analysis suggested that the RhoA/ROCK pathway was a downstream effector of AKR1C3, and exogenous PGD2 supplementation could reverse AKR1C3-mediated regulation of this pathway. We identified curcumin, a natural product with anti-cancer metabolic regulatory activity, as an upstream modulator that suppresses JUN expression, thereby activating the JUN/AKR1C3 axis and inhibiting malignant phenotypes in GBM cells. JUN/AKR1C3 axis influences glioma progression via modulating PGD2-mediated RhoA/ROCK Signaling.
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高影响因子
CELLULAR PHYSIOLOGY AND BIOCHEMISTRY
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2016
·Vol. 39
·期 4
·1391-1403
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IF 4.652
Zhang Lei,Jiang Guoliang,Zhao Xueling,Gong Yuekun
Background/Aims: We investigated the role of dimethyloxalylglycine (DMOG) in bone marrow mesenchymal stem cell (BMSC) osteogenesis mediated by RhoA/ROCK. Methods: BMSCs were cultured with and without DMOG and/or Y-27632 (ROCK1 inhibitor). Cell proliferation, alkaline phosphatase (ALP) levels, and calcium deposits were determined. The expression of Runx2, OSX, p-cofilin, RhoA, and GTP-bound RhoA was determined by real-time RT-PCR and Western blot. Rho-associated coiled-coil-containing protein kinase (ROCK) activity was determined by measuring the phosphorylation of myosin-binding subunit of myosin phosphatase using an ELISA kit. Actin morphology was observed by immunofluorescence. Results: After 24 h, DMOG (0.5 mM) increased the expression of GTP-bound RhoA (+141%, P < 0.001) and enhanced ROCK activity (315%, P < 0.001). DMOG (0.5 mM) enhanced ALP levels after 3, 7, and 21 days of osteogenic induction (all P < 0.001) and strengthened calcium deposition (P < 0.001). In addition, compared with controls, DMOG (0.5 mM) increased the mRNA levels of osteogenesis genes RUNX2 and OSX (all P < 0.001). Furthermore, compared with controls, DMOG increased the expression of p-cofilin (+57%, P < 0.001), which resulted in rearrangement of actin filaments. All these effects were abolished, at least in part, by Y-27632. Conclusion: DMOG promotes BMSC osteogenic differentiation via activation of RhoA/ROCK, suggesting clues for future therapies using BMSCs
研究领域:
干细胞生物学
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骨骼生物学
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细胞信号传导
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分子生物学
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DOI
PubMed
高影响因子
ACS Biomaterials Science & Engineering
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2024
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IF 5.4
Xiangyu Dong,Shan Su,Qian Sun,Peng Wang,Qian Hu,Qiang Wei
The extracellular matrix (ECM) plays a crucial role in regulating cellular behaviors and functions. However, the impact of ECM topography on muscle cell adhesion and differentiation remains poorly understood from a mechanosensing perspective. In this study, we fabricated aligned and random electrospun polycaprolactone (PCL) nanofibers to mimic the structural characteristics of ECM. Mechanism investigations revealed that the orientation of nanofibers promoted C2C12 polarization and myogenesis through Rac-related signaling pathways. Conversely, cells cultured on random fibers exhibited spreading behavior mediated by RhoA/ROCK pathways, resulting in enhanced stress fiber formation but reduced capacity for myogenic differentiation. Our findings highlight the critical role of an ECM structure in muscle regeneration and damage repair, providing novel insights into mechanosensing mechanisms underlying muscle injury diseases.
研究领域:
生物医学工程
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细胞生物学
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组织工程
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再生医学
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DOI
高影响因子
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