INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
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2024
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IF 7.7
Siqi Quan,Jingting Zhang,Lanyue Zhang,Na Li,Lijun Zhu,Xiuxia Sun,Jianxi Xiao
Type IV collagen , a principal constituent of basement membranes , consists of six distinct α chains that assemble into both ABC and AAB-type heterotrimers. While collagen-like peptides have been investigated for heterotrimer formation, the construction of ABC-type heterotrimeric collagen mimetic peptides remains a formidable challenge, primarily due to the intricate composition and arrangement of the chains. We have herein for the first time reported the development of a versatile triblock peptide system to mimic ABC-type heterotrimeric collagen stabilized by salt bridges. The triblock peptides A, B, and C incorporate functional natural type IV collagen sequences in the center, along with charged amino acids at their N and C-terminals. By leveraging electrostatic repulsion at these charged termini, the formation of homotrimers is effectively inhibited, while stable ABC-type heterotrimers are generated through the establishment of salt bridges between oppositely charged terminals. Circular dichroism (CD) spectroscopy demonstrated that peptides A, B, and C existed as individual monomers , while they effectively formed stable ABC-type heterotrimers upon being mixed at a molar ratio of 1:1:1. Additionally, fluorescence quenching results indicated that fluorescence-labeled peptides A′, B′, and C′ formed ABC-type heterotrimer, exhibiting comparable thermal stability as determined by CD spectroscopy. Molecular dynamics simulations elucidated the role of salt bridges between arginine and aspartic acid residues at N- and C-terminals in maintaining a unique chain register in the ABC-type heterotrimers. These triblock peptides offer a robust approach for replicating the structural and functional characteristics of type IV collagen, with promising applications in elucidating the biological roles and pathologies associated with heterotrimeric collagen.
研究领域:
生物化学
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分子生物学
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材料科学
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DOI
PubMed
高影响因子
Analytical Methods
·
2024
·Vol. 16
·期 15
·2248-2255
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IF 2.7
Xiaoling Fu,Fan Zhang,Fangda Zhen,Lian Duan,Jian Zhou,Jianguo Ma
Herein, a magnetic bead-based chemiluminescence assay is reported to detect type IV collagen (col-IV) in serum samples. Magnetic beads (MBs) exhibit biocompatibility. Taking advantage of this property, they were conjugated with the col-IV antibody. For the determination of col-IV, the interaction of the col-IV sample, anti-(col-IV)-alkaline phosphatase (anti-(col-IV)-ALP) and anti-col-IV-magnetic beads (anti-(col-IV)-MBs) was performed to generate chemiluminescence. Under the optimized conditions, the developed method displayed good linearity in the concentration range of 20–2000 ng mL−1 with the limit of 0.79 ng mL−1. The repeatability coefficient of variation (CV) for col-IV detection ranged from 3.16% to 7.50%. The col-IV level in samples collected from a hospital was assessed by the chemiluminescence assay. Satisfactory recoveries were obtained ranging from 93.30% to 100.14%. In conclusion, the magnetic bead-based chemiluminescence assay may be used as a routine and efficient tool to detect type IV collagen in clinical diagnosis.
研究领域:
医学诊断
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免疫学
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生物化学
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DOI
PubMed
高影响因子
Analytical Methods
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2019
·Vol. 11
·期 46
·5880-5885
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IF 2.378
Jiexia Chen,Guang-Chao Zhao,Yan Wei,Dexiang Feng
A signal-on photoelectrochemical (PEC) biosensing platform was developed here for the highly sensitive detection of a cancer marker type IV collagenase, which relied on the exciton energy transfer (EET) between CdTe quantum dots (QDs) and Ag nanoparticles (NPs) combined with the catalytic hydrolysis of a protease. A special sequence peptide chain with positively charged arginines at one end and a cysteine-labeled terminal at the other end, which could be modified with Ag NPs, was designed and synthesized. CdTe QDs and synthetic peptide were assembled onto the surface of indium–tin oxide (ITO) electrodes by means of a layer-by-layer self-assembly technology. The as-obtained modified electrodes generated a lower photocurrent under irradiation due to the effect of EET. The photocurrent intensity increased due to the addition of type IV collagenase, which could specifically hydrolytically cleave Gly–Pro–Ala, leading to Ag NPs being away from the electrode surface. Thus, a signal-on PEC biosensor could be obtained. Under optimum conditions, the PEC biosensor for type IV collagenase exhibited a linear range from 0.5 to 50 μg mL−1 and sensitivity of 96 ng mL−1. The peptide-QD-based PEC detection against type IV collagenase showed a promising potential for other protease or kinase detection when we changed the substrate of the peptide.
研究领域:
生物医学工程
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分析化学
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癌症诊断
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DOI
高影响因子
COLLOIDS AND SURFACES B-BIOINTERFACES
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2019
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IF 3.973
Chenglong Yu,Meiyi Xing,Shibo Sun,Guoping Guan,Lu Wang
Vascular basement membrane (VBM) is a thin layer of fibrous extracellular matrix linking endothelium, and collagen type IV (COL IV) is its main composition. VBM plays a crucial role in anchoring down the endothelium to its loose connective tissue underneath. For vascular grafts, constructing biomimetic VBMs on the luminal surface is thus an effective approach to improve endothelialization in situ . In the present work, three types of polycaprolactone (PCL) membranes were produced and characterized through cell counting kit-8 (CCK-8) assay, adhesion force and elastic modulus test to examine the influence of fiber diameter and membrane composition on vascular endothelial cell (EC) behaviors. The PCL membranes with finer fibers of 54.77 nm (PCL-54) could biomimic the nanotopography of VBMs more efficiently than 544.64 nm (PCL-544), and they were more suitable for Pig iliac endothelium cells (PIECs) adhesion and proliferation, meanwhile, inducing higher elastic modulus and adhesion force of PIECs. On this foundation, we further immobilized COL IV onto PCL-54 (PCL-COL IV) to biomimic VBMs compositionally. Results showed that PIECs on PCL-COL IV exhibited the highest viability and proliferation. Besides, quantitative data indicated that the elastic modulus of the PIECs on PCL-COL IV (4441.00 Pa) was as two times higher than that on PCL-54 (2312.26 Pa), and the adhesion force grew to 1120.99 pN from 673.58 pN of PIECs on PCL-54. In summary, the PCL-COL IV membranes show high similarity with the native VBMs in terms of structure and composition, suggesting a promising potential for surface modification to vascular grafts for improved endothelialization.
研究领域:
组织工程
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生物材料
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细胞生物学
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DOI
PubMed
高影响因子
Science China-Life Sciences
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2020
·Vol. 64
·期 3
·443-451
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IF 4.611
Luan Dongrui,Zhao Zengteng,Xia Dandan,Zheng Qiuling,Gao Xiaonan,Xu Kehua,Tang Bo
Sodium selenite has alleviating effects on liver fibrosis; however, its therapeutic molecular mechanism remains unclear. Herein, hydrogen selenide, a major metabolite of Na 2 SeO 3 , was tested to uncouple the sulfilimine bond in collagen IV, the biomarker of liver fibrosis. A mouse model of liver fibrosis was constructed via a CCl 4 -induced method, followed by the administration of 0.2 mg kg −1 Na 2 SeO 3 via gavage three times per week for 4 weeks. Changes in H 2 Se, NADPH, and H 2 O 2 levels were monitored in real time by using NIR-H 2 Se, DCI-MQ-NADPH, and H 2 O 2 probes in vivo , respectively. H 2 Se continuously accumulated in the liver throughout the Na 2 SeO 3 treatment period, but the levels of NADPH and H 2 O 2 decreased. The expression of collagen IV was analyzed through Western blot and liquid chromatography-mass spectrometry. Results confirmed that the sulfilimine bond of collagen IV in the fibrotic mouse livers could be broken by H 2 Se with the Na 2 SeO 3 treatment. Therefore, the therapeutic effect of Na 2 SeO 3 on liver fibrosis could be mainly attributed to H 2 Se that uncoupled the sulfilimine bond to induce collagen IV degradation. This study provided a reasonable explanation for the molecular mechanism of the in vivo function of Na 2 SeO 3 and the prevention of liver fibrosis by administering inorganic selenium.
研究领域:
药理学
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生物化学
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肝病学
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DOI
PubMed
高影响因子
Food & Function
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2024
·Vol. 15
·期 24
·11990-12006
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IF 5.1
Xilin Zhao,Songping Wang,Xuelan He,Wentao Wei,Kaipeng Huang
Our previous studies have demonstrated that ubiquitin-specific peptidase 22 (USP22) has the capacity to accelerate renal epithelial-to-mesenchymal transition (EMT) and promote the pathological progression of diabetic tubulointerstitial fibrosis (TIF) by regulating the ubiquitination of Snail1, an EMT transcription factor. Quercetin is a type of flavonol compound widely found in fruits and vegetables that has anti-inflammatory, antioxidant and anti-fibrosis effects. However, whether quercetin promotes the degradation of Snail1 and regulates the pathological progression of TIF by inhibiting USP22 requires further investigation. In this study, we found that quercetin significantly inhibited the expression of USP22 and Snail1 in high glucose (HG)-induced renal tubular epithelial cells (TECs), and reversed the expression of EMT-related proteins and inhibited the overproduction of fibronectin (FN) and Collage Type IV (Collagen IV) induced by high glucose. Additionally, quercetin blocked the deubiquitination of Snail1 mediated by USP22. Further study found that quercetin inhibited the interaction between USP22 and Snail1, thereby reducing the stability of Snail1. Furthermore, quercetin also reduced the protein levels of USP22 and Snail1 in the kidney tissue of diabetic mice and ameliorated renal function, delayed EMT and TIF. In conclusion, quercetin regulates the USP22-Snail1 signal pathway to inhibit the occurrence of EMT both in vitro and in vivo, and ultimately ameliorate the pathological progress of TIF.
研究领域:
肾病学
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分子生物学
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药理学
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DOI
PubMed
高影响因子
eLife
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2022
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IF 8.713
Zhenzhen Wang,Ziyu Zhai,Chunyu Chen,Xuejiao Tian,Zhen Xing,Panfei Xing,Yushun Yang,Junfeng Zhang,Chunming Wang,Lei Dong
Although fine particulate matter (FPM) in air pollutants and tobacco smoke is recognized as a strong carcinogen and global threat to public health, its biological mechanism for inducing lung cancer remains unclear. Here, by investigating FPM’s bioactivities in lung carcinoma mice models, we discover that these particles promote lung tumor progression by inducing aberrant thickening of tissue matrix and hampering migration of antitumor immunocytes. Upon inhalation into lung tissue, these FPM particles abundantly adsorb peroxidasin (PXDN) – an enzyme mediating type IV collagen (Col IV) crosslinking – onto their surface. The adsorbed PXDN exerts abnormally high activity to crosslink Col IV via increasing the formation of sulfilimine bonds at the NC1 domain, leading to an overly dense matrix in the lung tissue. This disordered structure decreases the mobility of cytotoxic CD8+ T lymphocytes into the lung and consequently impairs the local immune surveillance, enabling the flourishing of nascent tumor cells. Meanwhile, inhibiting the activity of PXDN abolishes the tumor-promoting effect of FPM, indicating the key impact of aberrant PXDN activity on the tumorigenic process. In summary, our finding elucidates a new mechanism for FPM-induced lung tumorigenesis and identifies PXDN as a potential target for treatment or prevention of the FPM-relevant biological risks.
研究领域:
肿瘤学
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免疫学
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环境健康
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分子生物学
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DOI
PubMed
高影响因子
Bioactive Materials
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2024
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IF 18
Jian Li,Jvhong Zhang,Pengcheng Yu,Han Xu,Meihui Wang,Zhebin Chen,Bo Yu,Jing Gao,Qiao Jin,Fan Jia,Jian Ji,Guosheng Fu
Vascular diseases seriously threaten human life and health. Exogenous delivery of nitric oxide (NO) represents an effective approach for maintaining vascular homeostasis during pathological events. However, the overproduction of reactive oxygen species (ROS) at vascular injury sites would react with NO to produce damaging peroxynitrite (ONOO − ) species and limit the therapeutic effect of NO. Hence, we design a ROS-responsive NO nanomedicine (t-PBA&NO NP) with ROS scavenging ability to solve the dilemma of NO-based therapy. t-PBA&NO NP targets NO and anti-oxidant ethyl caffeate (ECA) to the injury sites via collagen IV homing peptide. The ROS-triggered ROS depletion and ECA release potently alleviate local oxidative stress via ROS scavenging, endoplasmic reticulum and mitochondrial regulation. It subsequently maximizes vascular modulation effects of NO, without production of harmful compounds, reactive nitrogen species (RNS). Therefore, it significantly increases competitiveness of human umbilical vein endothelial cells (HUVECs) over human aortic smooth muscle cells (HASMCs) both in vitro and in vivo. The strategy proved effective in inducing faster re-endothelialization, inhibiting neointimal formation and restoring vascular homeostasis. The synergy between ROS depletion and NO therapy served as a new inspiration for the treatment of cardiovascular diseases and other ROS-associated illnesses.
研究领域:
药理学
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纳米技术
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心血管医学
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分子生物学
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治疗学
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产品关联
DOI
PubMed
高影响因子
ACS Sensors
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2024
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IF 8.2
Linge Nian,Wenhua Li,Chunxia Zhang,Lu Li,Guangrui Zhang,Jianxi Xiao
Hepatic fibrosis, the insidious progression of chronic liver scarring leading to life-threatening cirrhosis and hepatocellular carcinoma, necessitates the urgent development of noninvasive and precise diagnostic methodologies. Denatured collagen emerges as a critical biomarker in the pathogenesis of hepatic fibrosis. Herein, we have for the first time developed 3D-printed collagen capture chips for highly specific surface-enhanced Raman scattering (SERS) detection of denatured type I and type IV collagen in blood, facilitating the early diagnosis of hepatic fibrosis. Employing a novel blend of denatured collagen-targeting peptide-modified silver nanoparticle probes (Ag@DCTP) and polyethylene glycol diacrylate (PEGDA), we engineered a robust ink for the 3D fabrication of these collagen capture chips. The chips are further equipped with specialized SERS peptide probes, Ag@ICTP@R1 (S–I) and Ag@IVCTP@R2 (S–IV), tailored for the targeted detection of type I and IV collagen, respectively. The SERS chip platform demonstrated exceptional specificity and sensitivity in capturing and detecting denatured type I and IV collagen, achieving detection limits of 3.5 ng/mL for type I and 3.2 ng/mL for type IV collagen within a 10–400 ng/mL range. When tested on serum samples from hepatic fibrosis mouse models across a spectrum of fibrosis stages (S0–S4), the chips consistently measured denatured type I collagen and detected a progressive increase in type IV collagen concentration, which correlated with the severity of fibrosis. This novel strategy establishes a benchmark for the multiplexed detection of collagen biomarkers, enhancing our capacity to assess the stages of hepatic fibrosis.
研究领域:
生物医学工程
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分析化学
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肝病学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
iScience
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2021
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IF 5.458
Yuying Zhang,Anqi Guo,Cheng Lyu,Ran Bi,Zhaozhao Wu,Wenjing Li,Peng Zhao,Yudi Niu,Jie Na,Jianzhong Jeff Xi,Yanan Du
Summary It is still a challenge for synthesizing ‘cellular niche-mimics’ in vitro with satisfactory reproducibility and fidelity to recreate the natural niche components (e.g., extracellular matrices and soluble factors) for stem cell cultivation. Inspired by the massive amplification of hepatic progenitor cells during liver fibrosis in vivo , here we optimized the in vitro liver fibrotic niches and subsequently harvested their bioactive ingredients as niche extracts (NEs). The fibrosis-relevant NE marginally outperformed Matrigel for phenotype maintenance of human embryonic stem cell (hESC)-derived hepatoblasts (HBs) and recapitulation of the pathological angiogenesis of hESC-derived endothelial cells both in 2D culture and 3D liver organoids. Finally, defined NE components (i.e., collagen III, IV, IL-17, IL-18 and M-CSF) were resolved by the quantitative proteomics which exhibited advantage over Matrigel for multi-passaged HB expansion. The pathology-relevant and tissue-specific NEs provide innovative and generalizable strategies for the discovery of optimal cellular niche and bioactive niche compositions.
研究领域:
干细胞生物学
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组织工程
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细胞微环境
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蛋白质组学
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类器官培养
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DOI
PubMed
高影响因子
PLoS One
·
2025
·Vol. 20
·期 8
·e0329460
·
IF 2.6
Kan Tao,Huilin Zhu,Jing Wei
Skin aging is characterized by a loss of collagen. Collagen stimulates the secretion of extracellular matrix (ECM) components by skin fibroblasts, contributing to anti-wrinkle and skin-firming effects in cosmetic applications. However, the skin barrier poses a significant challenge to collagen absorption, hindering its dermal functionality. Rapid advancements in synthetic biology have enabled the development of recombinant human collagen (RHC) with controllable sequence and molecular weight, enhancing its potential cosmetic applications. Nonetheless, research on the ability of RHC to penetrate the skin and exert anti-aging effects remains limited, and its underlying mechanisms are largely unexplored. To address this gap, we selected low molecular weight recombinant human collagen peptide (LRHC) and evaluated its skin permeability and anti-aging mechanisms. Findings indicated that LRHC significantly promoted fibroblast proliferation and enhanced the transcription of collagen types I and type III. Furthermore, in photoaged nude mouse models, LRHC upregulated the expression of key basement membrane components, including collagen type IV (COL4), collagen type VII (COL7), collagen type XVII (COL17), integrin β4 (ITGB4), and laminin-332 (LN332, formerly LN5), resulting in increased collagen fiber density. Notably, LRHC demonstrated a dermal permeability rate of 74.7 ± 14.2% after 8 hours. Transcriptome sequencing revealed that LRHC may maintain cytoskeletal structure through activation of adherens junction signaling pathways and promote extracellular matrix (ECM) production through activation of transforming growth factor-beta (TGF-β) signaling pathways, thereby achieving anti-aging efficacy.. These findings confirm that LRHC can penetrate the dermis and exert anti-aging effects on skin, potentially through mechanisms mediated by adherens junction signaling pathways. As a functional active ingredient with anti-aging properties, LRHC holds significant potential for cosmetic applications.
研究领域:
化妆品科学
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皮肤科学
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分子生物学
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生物化学
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生物技术
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药理学
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细胞生物学
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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）