Advanced Materials Interfaces
·
2020
·Vol. 7
·期 12
·1902127
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IF 4.948
Shiwei Liu,Kai Li,Tao Hu,Xiaodong Wu,Haiyong Ao,Youtao Xie,Xuebin Zheng
The osteoblast-function associated integrin–ligand interactions are known to be dependent on divalent cations, but there is scarce information about the effect of Ca 2+ and Mg 2+ adsorption properties of an implant surface on integrin α 5 β 1 –fibronectin interactions and the subsequent osteoblast behavior. Cation adsorption properties are closely associated with the extent of structural defects in materials. Here, the birnessite-type MnO 2 coatings with different amounts of manganese vacancy ( V Mn ) are prepared on Ti substrates via hydrothermal treatment (denoted as 1M100-Ti, 5M100-Ti, and 5M120-Ti). The 5M120-Ti surface with hierarchical flower-like structure and the most stacked [MnO 6 ] layers possess the highest V Mn content, which is determined by the ratios of Mn 3+ /Mn 4+ and K/Mn. The increased V Mn content enhances the Ca 2+ and Mg 2+ adsorption properties of the birnessite coatings. When immersed in Ca 2+ /Mg 2+ aqueous solution, the birnessite coatings significantly promote fibronectin adsorption and the exposure of cell-binding domains on adsorbed fibronectin with 5M120-Ti showing the greatest enhancement. Accordingly, the 5M120-Ti surface provides more α 5 β 1 -integrin-specific instructions to MC3T3-E1 preosteoblasts capable of enhancing spreading and osteoblastic differentiation compared to two other samples. This study may provide a prospective approach of modulation of integrin–ligand interactions for controlling cell behavior by adjusting metal vacancies in metal oxides coatings.
研究领域:
材料科学
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生物医学工程
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细胞生物学
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DOI
高影响因子
MOLECULAR NUTRITION & FOOD RESEARCH
·
2022
·Vol. 66
·期 7
·2101088
·
IF 6.575
Hui-jian Chen,Xi-yue Yan,Ao Sun,Li Zhang,Jing Zhang,You-e Yan
Scope High-fat-diet (HFD) is an important factor in obesity. Extracellular matrix (ECM) regulates white adipose tissue (WAT), but its mechanism is unknown. Methods and Results This study uses three models—HFD-fed mice, human with obesity, and 3T3-L1 adipocytes with oleic acid (OA)/macromolecular crowders (MMC) treatment. Glucose and lipids metabolic disorders, increased collagen I/IV and laminin α2/4 (LAMA2/4), and upregulated integrins (ITGA1/ITGA7) – focal adhesion kinase (FAK) – c-Jun N-terminal kinase (JNK)/extracellular regulated protein kinase 1/2 (ERK1/2) signals in obese WAT from mice and human are observed. The upregulation of ECM – integrin – FAK signals is stronger in subcutaneous WAT than that in visceral WAT of mice, but these results are reversed in human. In vitro, oleic acid (OA) promotes lipid accumulation and upregulates collagen IV, LAMA4, and p-JNK. MMC is used to induce ECM deposition in adipocytes. MMC promotes adipocyte differentiation and integrins – FAK – JNK/ERK1/2 signals. When FAK phosphorylation is inhibited, downstream p-JNK is decreased. Inhibition of FAK phosphorylation reduces adipocyte differentiation, but MMC partially reverses this effect. Conclusion HFD-induced ECM deposition, whose signals are transmitted into adipocytes through upregulating ITGA1/ITGA7, activates the phosphorylation of intracellular FAK – JNK/ERK1/2 signals, and promotes adipogenesis in WAT. This mechanism provides novel therapeutic targets to treat obesity.
研究领域:
营养学
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细胞生物学
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分子生物学
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代谢紊乱
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肥胖研究
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产品关联
DOI
PubMed
高影响因子
PHYTOTHERAPY RESEARCH
·
2026
·
IF 8.1
Jing Qin,Huanhuan Huang,Mengzhen Xu,Lin Zhu,Haoli Liu,Xinyu Qian
Laminin promotes tumor progression, but its role in small-cell lung cancer (SCLC) remains unclear. Curcumol, a natural compound from Curcumae Rhizoma, has anti-tumor activity. Here, we tested the hypothesis that Curcumol disrupts Laminin–Integrin β1 interaction to suppress SCLC. SBC-2 and H69 cells were cultured on Laminin-coated substrates. Cell functions were assessed by Transwell migration, colony formation, and MTT assays. Molecular mechanisms were investigated through qRT-PCR, Western blot, molecular docking, Co-IP, and Dot blot assays. Target specificity was confirmed by Integrin β1 mutagenesis. The therapeutic efficacy of Curcumol was evaluated in xenograft mouse models. Laminin enhanced malignant phenotypes in SCLC cells, accompanied by the activation of FAK/ERK and TGF-β/Smad2/3 pathways. Curcumol inhibited the laminin-promoted malignant phenotypes and epithelial–mesenchymal transition (EMT) in SCLC cells and suppressed the expression of related proteins. Mechanistic studies revealed that Curcumol directly bound to Integrin β1, competitively inhibiting the binding of Laminin to Integrin β1 and the activation of downstream signaling. Target specificity was validated through mutagenesis studies, where Curcumol exhibited reduced efficacy in Integrin β1-mutant cells. In vivo, Curcumol (100 mg/kg, oral) attenuated Laminin-driven tumor growth, suppressed EMT and FAK/ERK signaling, with no detectable toxicity. Integrin β1 is a key mediator of Laminin's pro-tumorigenic effects in SCLC. Curcumol disrupts Laminin–Integrin β1 interaction, inhibits FAK/ERK signaling and EMT, and suppresses tumor progression, representing a promising therapeutic strategy.
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PubMed
高影响因子
Research
·
2026
·
IF 12.9
Ruidi Xia,Junlong Xue,Xinyu Liu,Mixiao Gui,Linjun Zhang,Yihua Cai,Zhengjie Shan,Guanqi Liu,Xuran Liao,Zhuofan Chen,Jieyun Xu,Zetao Chen
Decellularized extracellular matrix (dECM) leverages native architecture and bioactive components for tissue regeneration, yet its therapeutic efficacy is constrained by donor tissue maturity. While mature-tissue-derived dECM (Mat-dECM) lacks developmental signals, developmental-stage dECM (Dev-dECM) retains these cues but is limited by scarce sources and poor adaptability to adult environments. Here, we proposed postnatal maxillofacial odontogenic tissues as a novel Dev-dECM (pDev-dECM) source. Leveraging its unique trans-stage development—spanning embryonic crown formation to postnatal periodontal maturation—pDev-dECM balances developmental potency with adult environment adaptability. Multiomics comparative analysis revealed that pDev-dECM is enriched in arginylglycylaspartic-acid-containing proteins, which activate macrophage integrin αvβ5-mediated efferocytosis. This mechanism drives macrophage polarization toward regenerative M2 phenotypes, ensures adaptability to the adult environment, and reprograms mesenchymal stem cells to orchestrate developmental recapitulation. Consequently, pDev-dECM not only enabled in situ hierarchical regeneration of the periodontal complex but also facilitated cross-organ hierarchical regeneration in skin and muscle defect models. These findings demonstrate that pDev-dECM exerts spatiotemporal control over developmental recapitulation, establishing a universal biomaterial paradigm for multiscale tissue reconfiguration.
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PubMed
高影响因子
BIOLOGY OF REPRODUCTION
·
2025
·
IF 3
Zhang Yingying,Zhang Eryun,Li Ling,Ren Yongwei,Zhang Jinqiu,Zheng Qiutong,Sun Minya,Zhao Shaojie,Cui Yugui,Gu Ying,Xu Zhice
The risk of multiple placental thrombosis is significantly elevated in preeclampsia, and the vascular endothelium plays a vital role in coagulation processes through the secretion of Integrin alpha 2b, von Willebrand factor, and tissue factor. However, the underlying pathological mechanisms remain unclear. In this study, placental blood vessels were collected from both preeclampsia and normal pregnancies. Protein levels of Integrin alpha 2b were found to be up-regulated in preeclampsia samples compared to controls, indicating enhanced coagulation function in preeclampsia placental tissue. Additionally, higher cholesterol levels of plasma and lower AlkB homolog 1 expression in placental blood vessels of preeclampsia were found, overall DNA N6-methyldeoxyadenosine levels were up-regulated. Interestingly, the DNA N6-methyldeoxyadenosine level at the Integrin alpha 2b promoter was decreased. Cholesterol overload experiments in human umbilical vein endothelial cells demonstrated that cholesterol regulates the protein expression of AlkB homolog 1 and Integrin alpha 2b in a concentration-dependent manner. Furthermore, Integrin alpha 2b protein expression was increased following AlkB homolog 1 knockout, but no changes were observed when cholesterol was incubated with AlkB homolog 1 knockout cells. These findings provide critical insights into the roles of cholesterol levels, AlkB homolog 1, and Integrin alpha 2b in coagulation function within placental blood vessels. This information may contribute to further investigations of potential therapeutic targets and early prevention strategies for placental thrombosis in preeclampsia.
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
Nature Communications
·
2025
·Vol. 16
·期 1
·1-23
·
IF 15.7
Zhang Zhongyu,Zhao Zhengde,Huang Xiuyi,Zhou Lifang,Jiang Xin,Wu Haoliang,Liu Chenshu,Huang Kan,Wen Jielu,Liu Yunchong,Miller Michelle C.,Zhao Zihan,He Zhen,Wang Yuxin,Liu Siyu,Huang Lijin,Yuan Lining,Zeng Renli,Cen Zhipeng,Chen Anning,Chen Yanbo,Zeng Gang,Liu Wenzhou,Hong Xiaosi,Ren Meng,Yan Li,Zhang Yang,Guan Dongxian,Tian Xiaoyu,Cai Weikang,Tai Guihua,Mayo Kevin H.,Zhou Yifa,Li Zilun,Chen Sifan
Diabetic foot ulcers are severe diabetic complications, and promoting impaired angiogenesis is essential for wound healing. Pro-angiogenic galectin-3 is elevated in diabetic serum and promotes systemic insulin resistance that may impair wound healing. However, the exact role of galectin-3 in the regulation of diabetic wound healing remains unclear. Here, we demonstrate that galectin-3 promotes skin wound healing and angiogenesis via binding to its receptor integrin α5β1, and enhances downstream focal adhesion kinase phosphorylation by forming a liquid-liquid phase separation with integrin α5β1. Under diabetic conditions, aberrant accumulated advanced glycation end-products bind to galectin-3, blocking its interaction with integrin α5β1 and impairing angiogenesis. Topical treatment of recombinant galectin-3 in hydrogels promotes diabetic wound healing in rodents without causing systemic insulin resistance and synergizes with insulin. This study clarifies the binding of galectin-3 to integrin α5β1, instead of advanced glycation end-products, forming phase separation to promote angiogenesis and diabetic wound healing, laying the foundation for local galectin-3 therapy to treat diabetic foot ulcers.
研究领域:
糖尿病研究
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细胞生物学
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分子生物学
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伤口愈合
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血管生成
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糖生物学
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药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CELL CYCLE
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2021
·
IF 4.534
Limei Yan,Zeping He,Wei Li,Ning Liu,Song Gao
Rhophilin Rho GTPase binding protein 2 (P76RBE) belongs to rhophilin family of Rho-GTPase-binding proteins and is found to contribute to the development of diverse cancers. Data in Oncomine and Kaplan–Meier Plotter databases showed that P76RBE was upregulated in ovarian cancer tissues compared with normal tissues, and patients with high P76RBE expression had worse overall survival, which indicated P76RBE may be associated with the pathogenesis of ovarian cancer. This study aimed to investigate the role of P76RBE in ovarian cancer and to reveal the possible underlying mechanisms. The results demonstrated that P76RBE was highly expressed in ovarian cancer tissues and ovarian cancer cell lines. Functionally, silencing of P76RBE suppressed the proliferation, induced cell cycle arrest, and inhibited migration and invasion in OVCAR-3 and OV-90 cells, while overexpression of P76RBE showed opposite effects on A2780 cells. Mechanically, P76RBE silencing resulted in downregulation of integrin β1, accompanying the reduced NF-κB p65 phosphorylation and nuclear translocation. Importantly, integrin β1 knockdown effectively rescued the effects of P76RBE overexpression on ovarian cancer cells with suppressed proliferation, migration, and invasion. Additionally, in the xenograft tumors derived from OVCAR-3 and OV-90 cell lines, P76RBE knockdown inhibited tumor growth. Meanwhile, the expression of integrin β1 and NF-κB p65 phosphorylation was decreased. In summary, our findings indicate that P76RBE contributes to the progression of ovarian cancer through regulating the integrin β1/NF-κB signaling, and it may be a promising target for ovarian cancer therapy.
研究领域:
肿瘤学
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分子生物学
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细胞生物学
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DOI
PubMed
高影响因子
ANALYTICAL CHEMISTRY
·
2016
·
IF 5.886
Zhe Liu,Waner Chen,Yihong Li,Qien Xu
With a cocktail formulation of soybean milk as a green carbon source and TTDDA as a capping agent, integrin αvβ3-targeted C-dot nanocomposites (MB-CDs@NH-RGD) have been successfully fabricated via a facile microwaving protocol. Modification of the surface coating and RGD-conjugation endow their superior biocompatibility as well as highly specific targeting profile to αvβ3-overexpressed cell lines of MDA-MB231 and B16 as representative superficial malignant tumors. Meanwhile, the significant photothermal effect has been generated on irradiation of these targeted C-dot nanocomposites by a pulsed laser, which proved their eligibility for potential thermal ablation therapy. In vivo photoacoustic imaging using these C-dot nanocomposites as novel imaging probes verified their excellent targeting sensitivity and contrast enhancement. This exciting evidence implies a promising strategy to utilize them for multifunctional nanotheranostic purposes in combination with precision diagnosis and photothermal treatment against superficial malignant tumors.
研究领域:
纳米技术
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生物医学工程
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癌症研究
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材料科学
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成像科学
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DOI
PubMed
高影响因子
BIOMATERIALS
·
2021
·
IF 12.479
Chengyuan Huang,Xuan Zhao,Meiling Su,Zongning Yin
As glomerular cells, podocytes are the last line of defense for glomerular filtration barriers (GFB) and play a critical role in chronic kidney disease (CKD). Podocyte-targeted drug delivery is a promising direction in the treatment of CKD. In this study, we constructed four-arm star polymers conjugated with a novel linear RWrNM peptide. And poly ε-caprolactone (PCL) hydrophobic core and brush poly (2-hydroxyethyl methacrylate) (PHEMA) hydrophilic shell were synthesized by ROP and SET LRP polymerization. The PHEMA modified by succinic anhydride was coupled with the novel linear RWrNM peptide, and then the PCL hydrophobic core was loaded with dexamethasone acetate (Dexac) to form micelles with stable dimensions. Our findings showed that the novel micelles had an ultrasmall particle size of 16–30 nm. We, for the first time, showed that the specific affinity of the novel linear RWrNM peptide to primary podocytes (24.9 ± 1.7 times of the free RhB uptake) through the αvβ3 integrin receptor mediation was comparable to that of B16F10 cells (24.4 ± 1.2 times of the free RhB uptake). In vivo studies showed that the novel ultrasmall micelles possessed a significant kidney-targeted effect, excellent podocyte colocalization effect, and GFB permeability at 49%–60 % in normal SD rats . Besides, the novel ultrasmall micelles decreased the plasma elimination half-life of Dexac to 1.62–2.09 h and showed good safety in vitro and in vivo. Both in vitro and in vivo results demonstrated the novel ultrasmall micelles could be used as a promising drug delivery strategy for actively targeted therapy of CKD.
研究领域:
药学
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纳米技术
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生物医学工程
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药理学
·
肾脏生理学
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DOI
PubMed
高影响因子
BIOMATERIALS
·
2016
·
IF 8.387
Feng Li,Huihui Yan,Jiyao Wang,Cong Li,Jian Wu,Shengdi Wu,Shengxiang Rao,Xihui Gao,Qu Jin
Aims To explore the potential of a dendrimer nanoprobe labeled with cyclic arginine-glycine-aspartic acid pentapeptide (cRGDyK) as a magnetic resonance imaging (MRI) tracer to non-invasively differentiate the extent of liver fibrosis. Methods Synthetic dendrimer nanoprobes were labeled with cRGDyK (Den-RGD) to form a formulation of hepatic stellate cell (HSC)-specific MRI tracer. An MRI modality was employed to visualize hepatic Den-RGD deposition in a mouse model of liver fibrosis caused by thioacetamide treatment. Results Den-RGD bound to activated HSCs via integrin αvβ3 receptors. The labeling of nanoprobes with cRGDyK increased their affinity to and accelerated their uptake by activated HSCs. Most of intravenously administrated Den-RGD nanoprobes deposited in the fibrotic areas, and the deposited amount was paralleled with the severity of liver fibrosis. Majority of cells taking-up Den-RGD was found to be activated HSCs in fibrotic livers. An MRI modality using Den-RGD as a tracer demonstrated that the relative hepatic T1-weighed MR signal value was increased in parallel with the severity of liver fibrosis. Conclusion The extent of Den-RGD deposition reflects integrin αvβ3 expression in activated HSCs, and Den-RGD appears to be a useful formulation of MRI tracer and may non-invasively and quantitatively assess the extent of liver fibrosis.
研究领域:
医学影像学
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分子生物学
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肝病学
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DOI
PubMed
高影响因子
BIOCHEMICAL PHARMACOLOGY
·
2025
·
IF 5.6
Feng Li,Xinrong Fan,Bohao Wang,Jingyang Tong,Menglai Ling,Haibin Tong,Yumei Huang
Acute lung injury (ALI) in neonates presents a grave threat to infant health, characterized by a heightened risk of mortality. Phillyrin, an extraordinary constituent derived from a traditional Chinese medicinal herb Forsythia suspensa , has garnered considerable attention for its pronounced anti-inflammatory properties. However, its therapeutic potential for acute inflammatory diseases in neonates remains unclear. Therefore, our current study endeavors to assess the protective effects of phillyrin against lipopolysaccharide (LPS)-induced ALI in neonates and elucidate the underlying mechanisms. Phillyrin exhibited significant amelioration of lung damage in neonatal rats with LPS-induced ALI, accompanied by reductions in the total cell counts, neutrophil counts, and total protein level in bronchoalveolar lavage fluid (BALF). Notably, phillyrin substantially attenuated proinflammatory cytokine secretion and suppressed NF-κB activation in the lungs of neonatal ALI rats; however, it demonstrated inefficacy in mitigating LPS-induced cytokine secretion and NF-κB activation in vitro . Notably, phillyrin effectively inhibited β2 integrin-mediated neutrophil adhesion, migration, and chemotaxis. Moreover, phillyrin robustly suppressed β2 integrin engagement-induced actin polymerization and the Vav1/Rac1/PAK1/LIMK1/cofilin pathway. From a mechanistic standpoint, phillyrin exhibited direct interaction with β2 integrin, effectively antagonizing its function and significantly disrupting its binding affinity to intercellular adhesion molecule 1 (ICAM-1). This investigation unveils the promising therapeutic prospects of phillyrin as a novel compound against neonatal ALI.
研究领域:
药理学
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免疫学
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呼吸病学
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DOI
PubMed
高影响因子
EXPERIMENTAL ANIMALS
·
2022
·
IF 1.798
Guangquan Hu,Xiaojie Ding,Feng Gao,Jiehua Li
Myocardial infarction (MI) is a severe coronary artery disease resulted from substantial and sustained ischemia. Abnormal upregulation of calcium and integrin binding protein 1 (CIB1) has been found in several cardiovascular diseases. In this study, we established a mouse model of MI by permanent ligation of the left anterior descending coronary artery. CIB1 was upregulated in the heart of MI mice. Notably, CIB1 knockdown by intramuscular injection of lentivirus-mediated short hairpin RNA (shRNA) targeting Cib1 improved cardiac function and attenuated myocardial hypertrophy and infarct area in MI mice. MI-induced upregulation of α-SMA, vimentin, Collagen I, and Collagen III, which resulted in collagen production and myocardial fibrosis, were regressed by CIB1 silencing. In vitro, cardiac fibroblasts (CFs) isolated from mice were subjected to angiotensin II (Ang II) treatment. Inhibition of CIB1 downregulated the expression of α-SMA, vimentin, Collagen I, and Collagen III in Ang II-treated CFs. Moreover, CIB1 knockdown inhibited Ang II-induced phosphorylation of PI3K-p85 and Akt in CFs. The effect of CIB1 knockdown on Ang II-induced cellular injury was comparable to that of LY294002, a specific inhibitor of the PI3K/Akt pathway. We demonstrated that MI-induced cardiac hypertrophy, myocardial fibrosis, and cardiac dysfunction might be attributed to the upregulation of CIB1 in MI mice. Downregulation of CIB1 alleviated myocardial fibrosis and cardiac dysfunction by decreasing the expression of α-SMA, vimentin, Collagen I, and Collagen III via inhibiting the PI3K/Akt pathway. Therefore, CIB1 may be a potential target for MI treatment.
研究领域:
心脏病学
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分子生物学
·
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
危险品化学品经营许可证（带存储）