LANGMUIR
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2024
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IF 3.7
Xiaokai Pan,Juan Nie,Jiacheng Lei,Peng Wang,Kaikai Zheng,Qiang Wei,Xiaojing Liu
Understanding how the spatial distribution of adhesive ligands regulates cell behavior is crucial for designing biomaterials. This study investigates how precisely controlled ligand spacing affects cell spreading and integrin subtype engagement. Using engineered polyacrylamide hydrogels with gold nanoparticle arrays, we explored the impact of RGD ligand spacings (30 and 150 nm) on human mesenchymal stromal cells. Cells exhibited distinct morphological behaviors: smaller spacings promoted larger spreading areas, while larger spacings resulted in elongated shapes with reduced spreading. Mechanistically, we found that the α5β1 integrin, not the αvβ3 integrin, played a central role in mediating these responses, alongside lamellipodia formation. Our findings provide critical insights into the spatial sensing of ligands, highlighting the influence of ligand spacing on cellular mechanotransduction and integrin-specific responses. This work advances the understanding of cell-material interactions and offers potential strategies for designing biomaterials to guide cell behavior in tissue engineering.
研究领域:
细胞生物学
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生物材料科学
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组织工程
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生物物理学
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高影响因子
TRENDS IN BIOTECHNOLOGY
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2026
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IF 16.6
Fan Ding,Jingjing Xu,Yue Ma,Zhaoyang Yao,Jia Gao,Kangni Shang,Karsten Haupt,Guoqing Pan
Integrin plays a crucial role in human immune system activation and stem cell differentiation through interactions with the extracellular matrix (ECM). Reversible modulation of integrin signaling has illuminated the road toward broad-spectrum disease treatment and tissue regeneration. In this regard, an integrin-like decoy receptor, termed molecularly imprinted polymer (MIP), was synthesized via solid-phase imprinting to target the Arg-Gly-Asp (RGD) sequence, an integrin-binding motif abundantly present in the ECM. The MIP, with temperature-dependent RGD affinity, enabled dynamic intervention in integrin signaling, thereby modulating integrin-RGD-mediated immune response and cell differentiation. The MIP could, on demand, orchestrate macrophage phenotypes to display proinflammatory or anti-inflammatory traits, potentially beneficial at the early stage of tissue injury. Furthermore, stem cell fates could be controlled by MIP, showing potential to prevent hyperplasia caused by excessive differentiation. The proof-of-concept studies demonstrate the feasibility of MIP-based decoy receptors in the dynamic control of integrin signals and cell evolution, showing promise in tissue repair and related diseases.
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高影响因子
JOURNAL OF NANOBIOTECHNOLOGY
·
2025
·Vol. 23
·期 1
·1-20
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IF 12.6
Yang Jinghong,Li Runli,Wang Xiaoshuang,Lu Dongheng,Li Weichang,Wang Yan
Irregular alveolar bone defects pose persistent clinical challenges due to their complex morphology and the lack of biomaterials that simultaneously provide structural integrity, biocompatibility, and dynamic osteoinductive potential. Herein, we report a fiber-reinforced, dual-network hydrogel system (OHADN fiber@Yoda1 hydrogel) engineered to recapitulate mechanobiological cues for enhanced bone regeneration. This injectable hydrogel integrates oxidized hyaluronic acid (OHA) crosslinked with Yoda1-loaded PLGA-collagen fiber fragments and stabilized via catechol-Fe³⁺ coordination, forming a robust and self-healing structure. The fiber network enhances matrix stiffness and sustains Yoda1 release, promoting PIEZO1 activation in stem cells and enabling persistent mechanotransduction. In vitro, this system effectively regulates macrophage polarization, maintains cellular tension homeostasis, and significantly upregulates osteogenic markers via the PIEZO1–ITGα5 axis. Transcriptomic profiling and mechanistic validation revealed that focal adhesion and cytoskeletal signaling pathways are enriched upon hydrogel treatment. In a rat alveolar bone defect model, the OHADN fiber@Yoda1 hydrogel demonstrated superior bone volume restoration and trabecular architecture compared to conventional materials. This work presents a promising paradigm for spatiotemporal control of osteoimmune microenvironments through mechanoresponsive biomaterials.Graphical abstract
研究领域:
生物材料
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组织工程
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机械生物学
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再生医学
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生物医学工程
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PubMed
高影响因子
Frontiers of Medicine
·
2025
·
IF 3.5
Li Fengchan,Ni Haofu,Tang Fan,Lyu Jiaxin,Wu Lili,Ren Lijie,Lu Qiongyu,Zhao Shouming,Tang Chaojun,Zhu Li
Atherosclerosis is a chronic inflammatory disease driven by pathological processes such as macrophage foam cell formation. Semaphorin 7A (SEMA7A) is an immunoregulatory signaling molecule known to modulate immune responses and cellular adhesion. However, the contribution of macrophage-derived SEMA7A to atherogenesis has yet to be fully elucidated. In this study, we analyzed gene expression profiles of human mononuclear cells from the Gene Expression Omnibus (GEO) database and revealed highly expressed SEMA7A and its receptor integrin β1 in macrophages. The upregulation of SEMA7A and integrin β1 was also observed during the differentiation of THP-1 monocytes into macrophages. Mice with macrophage-specific deletion of Sema7a showed a 57.2% reduction in atherosclerotic lesion size and improved plaque stability in atherosclerosis mouse model compared to control mice. Mechanistically, macrophage SEMA7A promoted the expression of macrophage scavenger receptor 1 (MSR1) and lipid uptake mediated by integrin β1 and downstream JNK signaling pathway in macrophages. Notably, pharmacological inhibition of integrin β1 with integrin receptor antagonist GLPG0187 effectively suppressed atherosclerosis progression. These findings identify macrophage-derived SEMA7A as a key driver of atherosclerosis through a novel integrin β1/JNK/MSR1 axis, providing potential targets for the prevention and treatment of atherosclerosis.
研究领域:
心血管研究
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免疫学
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分子生物学
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炎症
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PubMed
高影响因子
COMPOSITES PART B-ENGINEERING
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2022
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IF 11.322
Zhimo Liu,Binfan Zhao,Liucheng Zhang,Shutong Qian,Jiayi Mao,Liying Cheng,Xiyuan Mao,Zhengwei Cai,Yuguang Zhang,Wenguo Cui,Xiaoming Sun
Integrin is a widely distributed adhesion molecule on cell membrane surface, which plays a role in transferring mechanical properties signals of the extracellular matrix into cells during cell adhesion to the extracellular matrix. In this study, by introducing long-chain polyethylene glycol molecules that can be photo-crosslinked into gelatin chains, ultra-soft hydrogel that can simulate soft tissue in vivo is constructed and stimulated by "low matrix stiffness" of the integrin signaling pathway, to promote the vascularization function of stem cells. The storage modulus of the ultra-soft hydrogel at room temperature is as low as 3.24 ± 0.18 Pa and as high as 40.83 ± 1.32 Pa. In vitro experiments showed that the stiffness of hydrogel affects the activation of the phosphorylation of VEGFR by regulating the phosphorylation of integrin and further controls the activation of the ERK pathway, thus regulating the vascularization of ADSCs . In vivo experiments have proved that ADSCs encapsulated in PEG-Gel have excellent performance in repairing skin flaps. The ultra-soft hydrogel can promote the vascularization of ADSCs by activating the "extracellular matrix stiffness-integrin-VEGFR-ERK" regulatory pathway, which is a potential regenerative repair material for promoting the application of stem cells in skin flap repair.
研究领域:
生物材料
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组织工程
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干细胞生物学
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再生医学
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DOI
高影响因子
Drug Design Development and Therapy
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2022
·
IF 4.319
Yi Zhang,Xiujin Shi,Jialun Han,Wenxing Peng,Zhenwei Fang,Yang Zhou,Xiaoyu Xu,Jie Lin,Fucheng Xiao,Limin Zhao,Yang Lin
Introduction As the primary immune cells, macrophages play a key role in atherosclerotic progression. M2 macrophage polarization has been reported to promote tissue repair and attenuate plaque formation upon the expression of anti-inflammatory factors. Convallatoxin (CNT) is a natural cardiac glycoside with anti-inflammatory pharmacological properties. However, whether CNT protects against atherosclerosis (AS) and underlying mechanisms is unknown. This work was designed to explore the potential effects of CNT on atherosclerosis.Methods In this study, Apolipoprotein E deficiency (ApoE−/-) mice fed with high-fat diet were established, and CNT (50 or 100 μg/kg) were intragastrically administrated for 12 weeks every day. In vitro, RAW264.7 macrophages stimulated with ox-LDL were treated with CNT (50 or 100 nM) for 24 h. The specific PPARγ antagonist, GW9662, was used to block the PPARγ signaling pathway in vitro. Then, the atherosclerotic lesions, macrophage polarization markers, inflammatory cytokines and PPARγ signaling pathway were examined in further examinations.Results Our results showed that the atherosclerotic lesions were reduced by CNT, as demonstrated by the downregulation of serum lipid level and aortic plaque area in AS mice. Furthermore, we found that CNT treatment promoted the expression of M2 macrophage markers (Arg1, Mrc1, Retnla and Chi3l3), and decreased the levels of pro-inflammatory cytokines (IL-6 and TNF-α), accompanied by the increase of anti-inflammatory factor (IL-10) in aortic vessels of AS mice. In ox-LDL-induced RAW264.7 cells, CNT administration also facilitated macrophages polarizing towards M2 subtype and inhibited inflammatory responses. Furthermore, both the in vivo and in vitro experiments showed CNT could increase the expression of PPARγ, Integrin αv and Integrin β5, and GW9662 could block CNT-induced M2 macrophage polarization.Conclusion Taken together, these data suggest that CNT may promote M2 macrophage polarization to exert an anti-atherosclerotic effect, partially through activating PPARγ-Integrin αvβ5 signaling pathway.
研究领域:
心血管疾病
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免疫学
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药理学
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细胞生物学
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分子生物学
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DOI
PubMed
高影响因子
ACS Applied Materials & Interfaces
·
2016
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IF 7.145
Ye Tian,Sijia Gao,Man Wu,Xiangxiang Liu,Jing Qiao,Quan Zhou,Shidong Jiang,Zhongwei Niu
For cancer therapy, viruses have been utilized as excellent delivery vehicles because of their facile transfection efficiency in their host cells. However, their inherent immunogenicity has become the major obstacle for their translation into approved pharmaceuticals. Herein, we utilized rodlike plant virus, tobacco mosaic virus (TMV), which is nontoxic to mammals and mainly infects tobacco species, as anticancer nanorod-drug vector for cancer therapy study. Doxorubicin (DOX) was installed in the inner cavity of TMV by hydrazone bond, which enabled the pH-sensitive drug release property. Conjugation of cyclic Arg-Gly-Asp (cRGD) on the surface of TMV can enhance HeLa cell uptake of the carrier via the integrin-mediated endocytosis pathway. Comparing with free DOX, the cRGD-TMV-hydra-DOX vector had similar cell growth inhibition and much higher apoptosis efficiency on HeLa cells. Moreover, the in vivo assay assumed that cRGD-TMV-hydra-DOX behaved similar antitumor efficiency but much lower side effect on HeLa bearing Balb/c-nu mice. Our work provides novel insights into potentially cancer therapy based on rodlike plant viral nanocarriers.
研究领域:
生物技术
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纳米技术
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药学
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癌症研究
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DOI
PubMed
高影响因子
Advanced Science
·
2023
·
IF 15.1
Bingyang Dai,Yuwei Zhu,Xu Li,Zuru Liang,Shunxiang Xu,Shian Zhang,Zhe Zhang,Shanshan Bai,Wenxue Tong,Mingde Cao,Ye Li,Xiaobo Zhu,Wei Liu,Yuantao Zhang,Liang Chang,Patrick Shu-hang Yung,Kevin Ki-wai Ho,Jiankun Xu,To Ngai,Ling Qin
The knowledge of osteoarthritis (OA) has nowadays been extended from a focalized cartilage disorder to a multifactorial disease. Although recent investigations have reported that infrapatellar fat pad (IPFP) can trigger inflammation in the knee joint, the mechanisms behind the role of IPFP on knee OA progression remain to be defined. Here, dysregulated osteopontin (OPN) and integrin β 3 signaling are found in the OA specimens of both human and mice. It is further demonstrated that IPFP-derived OPN participates in OA progression, including activated matrix metallopeptidase 9 in chondrocyte hypertrophy and integrin β 3 in IPFP fibrosis. Motivated by these findings, an injectable nanogel is fabricated to provide sustained release of siRNA Cd61 ( RGD− Nanogel/siRNA Cd61 ) that targets integrins. The RGD− Nanogel possesses excellent biocompatibility and desired targeting abilities both in vitro and in vivo. Local injection of RGD− Nanogel/siRNA Cd61 robustly alleviates the cartilage degeneration, suppresses the advancement of tidemark, and reduces the subchondral trabecular bone mass in OA mice. Taken together, this study provides an avenue for developing RGD− Nanogel/siRNA Cd61 therapy to mitigate OA progression via blocking OPN-integrin β 3 signaling in IPFP.
研究领域:
骨科
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分子生物学
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纳米技术
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风湿病学
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DOI
PubMed
高影响因子
Frontiers in Immunology
·
2022
·
IF 8.786
Sun Xiaoxi,Huang Bing,Pan Yuping,Fang Jinhua,Wang Hefeng,Ji Yanru,Ling Yingchen,Guo Pei,Lin Jiangguo,Li Quhuan,Fang Ying,Wu Jianhua
Activation of integrins is crucial for recruitment of flowing leukocytes to inflammatory or injured vascular sites, but their spatiotemporal characteristics are incompletely understood. We discovered that β2-integrin activation over the entire surface of neutrophils on immobilized P-selectin occurred via mitogen-activated protein kinase (MAPK) or non-MAPK signaling with a minute-level timescale in a force-dependent manner. In flow, MAPK signaling required intracellular Ca2+ release to activate integrin within 2 min. Integrin activation via non-MAPK signaling occurred first locally in the vicinity of ligated P-selectin glycoprotein ligand-1 (PSGL-1) within sub-seconds, and then over the entire cell surface within 1 min in an extracellular Ca2+ influx-dependent manner. The transition from a local (but rapid) to global (but slow) activation mode was triggered by ligating the freshly activated integrin. Lipid rafts, moesin, actin, and talin were involved in non-MAPK signaling. Fluid loads had a slight effect on local integrin activation with a second-level timescale, but served as enhancers of global integrin activation.
研究领域:
免疫学
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细胞生物学
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生物物理学
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产品关联
DOI
PubMed
高影响因子
Cell Metabolism
·
2024
·
IF 27.7
Kan Huang,Zilun Li,Xi He,Jun Dai,Bingding Huang,Yongxia Shi,Dongxiao Fan,Zefeng Zhang,Yunchong Liu,Na Li,Zhongyu Zhang,Jiangyun Peng,Chenshu Liu,Renli Zeng,Zhipeng Cen,Tengyao Wang,Wenchao Yang,Meifeng Cen,Jingyu Li,Shuai Yuan,Lu Zhang,Dandan Hu,Shuxiang Huang,Pin Chen,Peilong Lai,Liyan Lin,Jielu Wen,Zhengde Zhao,Xiuyi Huang,Lining Yuan,Lifang Zhou,Haoliang Wu,Lihua Huang,Kai Feng,Jian Wang,Baolin Liao,Weiping Cai,Xilong Deng,Yueping Li,Jianping Li,Zhongwei Hu,Li Yang,Jiaojiao Li,Youguang Zhuo,Fuchun Zhang,Lin Lin,Yifeng Luo,Wei Zhang,Qianlin Ni,Xiqiang Hong,Guangqi Chang,Yang Zhang,Dongxian Guan,Weikang Cai,Yutong Lu,Fang Li,Li Yan,Meng Ren,Linghua Li,Sifan Chen
Thrombosis represents the leading cause of death and disability upon major adverse cardiovascular events (MACEs). Numerous pathological conditions such as COVID-19 and metabolic disorders can lead to a heightened thrombotic risk; however, the underlying mechanisms remain poorly understood. Our study illustrates that 2-methylbutyrylcarnitine (2MBC), a branched-chain acylcarnitine, is accumulated in patients with COVID-19 and in patients with MACEs. 2MBC enhances platelet hyperreactivity and thrombus formation in mice. Mechanistically, 2MBC binds to integrin α2β1 in platelets, potentiating cytosolic phospholipase A2 (cPLA2) activation and platelet hyperresponsiveness. Genetic depletion or pharmacological inhibition of integrin α2β1 largely reverses the pro-thrombotic effects of 2MBC. Notably, 2MBC can be generated in a gut-microbiota-dependent manner, whereas the accumulation of plasma 2MBC and its thrombosis-aggravating effect are largely ameliorated following antibiotic-induced microbial depletion. Our study implicates 2MBC as a metabolite that links gut microbiota dysbiosis to elevated thrombotic risk, providing mechanistic insight and a potential therapeutic strategy for thrombosis.
研究领域:
心血管研究
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微生物组学研究
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血栓机制
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代谢组学
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PubMed
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JOURNAL OF ETHNOPHARMACOLOGY
·
2024
·
IF 4.8
Weilai Yu,Boyang Li,Luxi Chen,Qiu Chen,QingQing Song,Xiaosheng Jin,Yandan Yin,Haibin Tong,Liwei Xue
Ethnopharmacological relevance Dendrobium, recognized as “Shihu” in traditional Chinese medicine, holds a rich history of medicinal utilization documented in the Chinese Pharmacopoeia. Ancient texts like “Shen Nong Ben Cao Jing” extol Dendrobium 's virtues as a superior herbal medicine fortifying “Yin” and invigorating the five viscera. Dendrobium is extensively employed for the treatment of gastrointestinal inflammatory disorders, showcasing significant therapeutic efficacy, particularly against ulcerative colitis (UC), within the realm of Chinese ethnopharmacology. Dendrobium plays crucial pharmacological roles due to its rich content of polysaccharides, alkaloids, phenanthrenes, and bibenzyls. Gigantol, a prominent bibenzyl compound, stands out as one of the most vital active constituents within Dendrobium , the gigantol content of Dendrobium leaves can reach approximately 4.79 μg/g. Its significance lies in being recognized as a noteworthy anti-inflammatory compound derived from Dendrobium . Aim of the study Given the pivotal role of gigantol as a primary active substance in Dendrobium , the therapeutic potential of gigantol for gastrointestinal diseases remains enigmatic. Our present investigation aimed to evaluate the therapeutic effects of gigantol on dextran sulfate sodium (DSS)-induced colitis and reveal its potential mechanism in countering UC activity. Materials and methods The protective efficacy of gigantol against colitis was assessed by examining the histopathological changes and conducting biochemical analyses of colon from DSS-challenged mice. Assessments focused on gigantol's impact on improving the intestinal epithelial barrier and its anti-inflammatory effects in colonic tissues of colitis mice. Investigative techniques included the exploration of the macrophage inflammatory signaling pathway via q PCR and Western blot analyses. In vitro studies scrutinized macrophage adhesion, migration, and chemotaxis utilizing transwell and Zigmond chambers. Furthermore, F-actin and Rac1 activation assays detailed cellular cytoskeletal remodeling. The potential therapeutic target of gigantol was identified and validated through protein binding analysis, competitive enzyme-linked immunosorbent assay (ELISA), cellular thermal shift assay (CETSA), and drug affinity responsive target stability (DARTS) assay. The binding sites between gigantol and its target were predicted via molecular docking. Results Gigantol ameliorated symptoms of DSS-induced colitis, rectified damage to the intestinal barrier, and suppressed the production of pro-inflammatory cytokines in colonic tissues. Intriguingly, gigantol significantly curtailed NF-κB signaling activation in the colons of DSS-induced colitis mice. Notably, gigantol impaired the β2 integrin-dependent adhesion and migratory capacity of RAW264.7 cells. Moreover, gigantol notably influenced the cytoskeleton remodeling of RAW264.7 cells by suppressing Vav1 phosphorylation and Rac1 activation. Mechanistically, gigantol interacted with β2 integrin, subsequently diminishing binding affinity with intercellular adhesion molecule-1 (ICAM-1). Conclusions In conclusion, these findings elucidate that gigantol ameliorates DSS-induced colitis by antagonizing β2 integrin-mediated macrophage adhesion, migration, and chemotaxis, thus it may impede macrophage recruitment and infiltration into colonic tissues. This study suggests that gigantol shows promise as a viable candidate for clinical colitis therapy.
研究领域:
药理学
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免疫学
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炎症性肠病
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传统中药
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分子生物学
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DOI
PubMed
高影响因子
Materials Today Bio
·
2025
·
IF 10.2
Xiaoying Feng,Ling Dai,Yanfang Guo,Liuting Zhong,Yuxiu Zheng,Senling Feng,Liping Cao,Zhongwen Yuan
Intrahepatic cholestasis in pregnancy (ICP) is a characteristic disease during the perinatal period; however, its therapy remains unsatisfactory, and the pathogenesis remains unclear. The ameliorative effect of naturally occurring quercetin 7-rhamnoside (Q7R) in cholestasis has been established. In this study, we aimed to establish a nanoparticle-based peptide, A20FMDV2-modified liposome (t-QL), to encapsulate and deliver Q7R. Q7R bioavailability improved significantly when liposomes were used as carriers. This peptide A20FMDV2-modified nanosystem targeted integrin αvβ6 on biliary epithelial cells and improved stillbirth rates and liver function indicators better than free Q7R without a carrier. Q7R improved ICP by regulating mitochondrial function and bile metabolism. Our nanosystem provides a promising nanotherapeutic strategy for applying Q7R in ICP. We also elucidated a therapeutic mechanism underlying the action of ICP by simultaneously targeting mitochondrial structure and function, as well as bile acid metabolism.
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高影响因子
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