Visualizing collagen proteolysis by peptide hybridization: From 3D cell culture to in vivo imaging

Bennink, Lucas L.; Li, Yang; Kim, Bumjin; Shin, Ik Jae; San, Boi Hoa; Zangari, Maurizio; Yoon, Donghoon; Yu, S. Michael

doi:10.1016/j.biomaterials.2018.08.039

Cited by 63 publications

(74 citation statements)

References 49 publications

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“…We next hypothesized that the absence of DO would lead to presentation of altered quantities of certain pMHCII molecules, thereby affecting thymic deletion [65]. Enumeration of CD4 T-cell precursor frequencies for immunodominant epitopes of two self-antigens, i.e., CII(280-294), known to be highly stable, yet DM-sensitive, and MOG (38)(39)(40)(41)(42)(43)(44)(45)(46)(47)(48)(49)(50)(51), postulated to be DMresistant, supported our hypothesis. DO-KO mice hold an increased PF of MOG(38-51)-specific CD4 T cells, consistent with a faulty thymic deletion.…”

Section: Discussionmentioning

confidence: 59%

“…Recently, a caged collagen mimetic peptide (CMP) probe that specifically binds to denatured collagen actively undergoing degradation has been defined [46][47][48]. This useful tool has further been developed for tracking collagen remodeling activity in vivo [49][50][51][52]. Of particular interest is that alongside the labeled CMP probe, additional probes conjugated to antibodies specific to different cell markers, such as CD4 or labeled tetramers, can be used simultaneously.…”

Section: Dr1 + Do-ko Mice Are More Susceptible To the Development Of Ramentioning

confidence: 99%

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Lack of the MHC class II chaperone H2-O causes susceptibility to autoimmune diseases

et al. 2020

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DO (HLA-DO, in human; murine H2-O) is a highly conserved nonclassical major histocompatibility complex class II (MHC II) accessory molecule mainly expressed in the thymic medulla and B cells. Previous reports have suggested possible links between DO and autoimmunity, Hepatitis C (HCV) infection, and cancer, but the mechanism of how DO contributes to these diseases remains unclear. Here, using a combination of various in vivo approaches, including peptide elution, mixed lymphocyte reaction, T-cell receptor (TCR) deep sequencing, tetramer-guided naïve CD4 T-cell precursor enumeration, and wholebody imaging, we report that DO affects the repertoire of presented self-peptides by B cells and thymic epithelium. DO induces differential effects on epitope presentation and thymic selection, thereby altering CD4 T-cell precursor frequencies. Our findings were validated in two autoimmune disease models by demonstrating that lack of DO increases autoreactivity and susceptibility to autoimmune disease development. Lack of the MHC Class II chaperone H-2O causes susceptibility to autoimmune diseases PLOS Biology | https://doi.org/10.1371/journal.pbio.3000590 February 18, 2020 3 / 29Fig 2. Naïve DO-KO mice have an expanded CD4 T-cell compartment as well as increased expression of Tregs. (A) Breakdown of T-cell compartment in the spleens of naïve DO-WT (white) and DO-KO (red) mice. N = 8 mice per group. Data are represented as mean ± SEM. (B). Subdivision of the CD4 T-cell compartment showed that DO-KO mice have increased percentage of CD4 + CD25 + -expressing cells. N = 8 mice per group. Data are represented as mean ± SEM. (C). Naïve expression of the Foxp3 transcription factor in naïve CD4 + T cells from DO-WT (white) and DO-KO (red) mice. N = 21 mice per group. Experimental results depicted in this figure can be found in S2 Data. Data are represented as mean ± SEM. DO, HLA-DO; Foxp3, forkhead box P3; KO, knockout; Treg, regulatory T cell; WT, wild-type. https://doi.org/10.1371/journal.pbio.3000590.g002 Lack of the MHC Class II chaperone H-2O causes susceptibility to autoimmune diseases PLOS Biology | https://doi.org/10.1371/journal.pbio.3000590 February 18, 2020 5 / 29 mice. (A) Representative curves showing the time course of disease development in DO-KO (red) and DO-WT mice (white). N = 5 mice per group, representative of >15 repeat experiments. Score system: 0 = no symptoms, 1 = limp tail, 2 = limp tail + partial hind limb paralysis, 3 = limp tail + total Lack of the MHC Class II chaperone H-2O causes susceptibility to autoimmune diseases PLOS Biology | https://doi.EAE was induced as previously described in both DO-WT and DO-KO mice. Mice were humanely killed on Day 17 of disease, brains and spinal columns were pooled, and infiltrating Lack of the MHC Class II chaperone H-2O causes susceptibility to autoimmune diseases PLOS Biology | https://doi.

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Section: Discussionmentioning

confidence: 59%

Section: Dr1 + Do-ko Mice Are More Susceptible To the Development Of Ramentioning

confidence: 99%

Lack of the MHC class II chaperone H2-O causes susceptibility to autoimmune diseases

et al. 2020

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“…Collagen can also be used for the imaging of targeted sites. Imaging of the collagen content and arrangement is conducive to the assessment of tissue stiffness, metabolism, and drug resistance [196][197][198], and technology to utilize these data is currently under development [199]; for instance, magnetic resonance apparent diffusion coefficient values were used to indicate a negative correlation of collagen with esophageal SCC cells [200]. The label-free Raman spectroscopic measurements used to distinguish radiation-sensitive tumors were based on differences in collagen content [201].…”

Section: Subtype Of Mmps Associated Collagen Pathological Functions Omentioning

confidence: 99%

The role of collagen in cancer: from bench to bedside

et al. 2019

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Collagen is the major component of the tumor microenvironment and participates in cancer fibrosis. Collagen biosynthesis can be regulated by cancer cells through mutated genes, transcription factors, signaling pathways and receptors; furthermore, collagen can influence tumor cell behavior through integrins, discoidin domain receptors, tyrosine kinase receptors, and some signaling pathways. Exosomes and microRNAs are closely associated with collagen in cancer. Hypoxia, which is common in collagen-rich conditions, intensifies cancer progression, and other substances in the extracellular matrix, such as fibronectin, hyaluronic acid, laminin, and matrix metalloproteinases, interact with collagen to influence cancer cell activity. Macrophages, lymphocytes, and fibroblasts play a role with collagen in cancer immunity and progression. Microscopic changes in collagen content within cancer cells and matrix cells and in other molecules ultimately contribute to the mutual feedback loop that influences prognosis, recurrence, and resistance in cancer. Nanoparticles, nanoplatforms, and nanoenzymes exhibit the expected gratifying properties. The pathophysiological functions of collagen in diverse cancers illustrate the dual roles of collagen and provide promising therapeutic options that can be readily translated from bench to bedside. The emerging understanding of the structural properties and functions of collagen in cancer will guide the development of new strategies for anticancer therapy.

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“…9 Finally, the HflpOH monomer is readily accessible from natural HHypOH by an S N 2 reaction. 35 We note that CMPs containing flp-Hyp-Gly units have been examined previously, 36,37 though in contexts distinct from those described herein. For example, (flpHypGly) 9 was found to form however, produces extremely unfavorable interactions, even when its neighbor is Pro (IE = 13.8 kcal mol −1 ).…”

Section: Resultsmentioning

confidence: 76%

“…This incompatibility is consistent with the low thermostability of triple helices with clpProGly units, 34 a stable triple helix at ambient temperature, complicating its use in biological contexts. 37 Hence, we examined a shorter peptide: (flpHypGly) 7 .…”

Section: Resultsmentioning

confidence: 99%

Optimization of interstrand interactions enables burn detection with a collagen-mimetic peptide

et al. 2019

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Visualizing collagen proteolysis by peptide hybridization: From 3D cell culture to in vivo imaging

Cited by 63 publications

References 49 publications

Lack of the MHC class II chaperone H2-O causes susceptibility to autoimmune diseases

Lack of the MHC class II chaperone H2-O causes susceptibility to autoimmune diseases

The role of collagen in cancer: from bench to bedside

Optimization of interstrand interactions enables burn detection with a collagen-mimetic peptide

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