Collagen-binding Protein Research Articles

Relationship between Streptococcus mutans expressing Cnm in the oral cavity and non-alcoholic steatohepatitis: a pilot study

BackgroundNon-alcoholic steatohepatitis (NASH) is a severe state of non-alcoholic fatty liver disease (NAFLD), which is pathologically characterised by steatosis, hepatocyte ballooning, and lobular inflammation. Host–microbial interaction has gained attention as...

A collagen-binding protein enables molecular imaging of kidney fibrosis in vivo

Pathological deposition of collagen is a hallmark of kidney fibrosis. To illustrate this process we employed multimodal optical imaging to visualize and quantify collagen deposition in murine models of kidney fibrosis (ischemia-reperfusion or unilateral ureteral obstruction) using the collagen-binding adhesion protein CNA35. For invivo imaging, we used hybrid computed tomography-fluorescence molecular tomography and CNA35 labeled with the near-infrared fluorophore Cy7. Upon intravenous injection, CNA35-Cy7 accumulation was significantly higher in fibrotic compared to non-fibrotic kidneys. This difference was not detected for a non-specific scrambled version of CNA35-Cy7. Exvivo, on kidney sections of mice and patients with renal fibrosis, CNA35-FITC co-localized with fibrotic collagen type I and III, but not with the basement membrane collagen type IV. Following intravenous injection, CNA35-FITC bound to both interstitial and perivascular fibrotic areas. In line with this perivascular accumulation, we observed significant perivascular fibrosis in the mouse models and in biopsy sections from patients with chronic kidney disease using computer-based morphometry quantification. Thus, molecular imaging of collagen using CNA35 enabled specific non-invasive quantification of kidney fibrosis. Collagen imaging revealed significant perivascular fibrosis as a consistent component next to the more commonly assessed interstitial fibrosis. Our results lay the basis for further probe and protocol optimization towards the clinical translation of molecular imaging of kidney fibrosis.

Probiotic Lactobacillus and Bifidobacterium strains possess safety characteristics, antiviral activities and host adherence factors revealed by genome mining.

Probiotics belonging to Lactobacillus and Bifidobacterium spp. have been exploited for their health benefits in treatment and prevention of many pathological conditions and promoting human health. Recent advances in understanding probiotics-human interaction through microbiome research in the context of various medical conditions suggest their provisional role in preventive, personalized, and predictive medicine. To streamline their application in disease prevention, development of personalized-based treatments, or their use as biomarkers for predictive diagnosis, in vitro screening for strains with potential probiotic properties should be performed. In this work, we aimed to emphasize the probiotic features of four Lactobacillus and two Bifidobacterium probiotic strains which showed antagonistic properties against microbial pathogens. Firstly, cytotoxicity assessment of cell-free preparations from these strains was performed using a baby hamster kidney (BHK) cells and cell viability was measured by means of sulfo-rhodamine B stain. Secondly, Newcastle disease (ND) and infectious bursal disease (IBD) viruses which pose a great threat in infected poultry were used for assessing antiviral activity of probiotics. Thirdly, the genomes of six probiotic strains were used to identify genes encoding host adherence factors that mediate interaction with human tissues. Probiotic preparations exhibited insignificant toxicity as indicated by the high survival rate of BHK cells (surviving fraction varied from 0.82 to 0.99) as compared to the untreated control. Cell-free preparations of probiotics mixed with equal volume of ND and IBD viruses (106 and 104 Tissue Culture Infectious Dose 50, respectively) reduced the titer of ND and IBD viruses on chicken embryo fibroblast cells. Genome mining analysis revealed that the draft genomes of these strains were predicted to encode LPXTG-containing proteins, surface layer proteins, tight adherence pili, sortase-dependent pili, fibronectin, or collagen binding proteins and other factors that adhere to human tissues such as mucus. Such adherence factors enable probiotic bacteria to interact and colonize the host. Taken together, safety privileges, antiviral activities, and genomically encoded host interaction factors confirmed probiotic features of the six probiotic strains and their potential in promoting human health.

Molecular underpinnings of integrin binding to collagen-mimetic peptides containing vascular Ehlers–Danlos syndrome–associated substitutions

Collagens carry out critical extracellular matrix (ECM) functions by interacting with numerous cell receptors and ECM components. Single glycine substitutions in collagen III, which predominates in vascular walls, result in vascular Ehlers-Danlos syndrome (vEDS), leading to arterial, uterine, and intestinal rupture and an average life expectancy of <50 years. Collagen interactions with integrin α2β1 are vital for platelet adhesion and activation; however, how these interactions are impacted by vEDS-associated mutations and by specific amino acid substitutions is unclear. Here, we designed collagen-mimetic peptides (CMPs) with previously reported Gly → Xaa (Xaa = Ala, Arg, or Val) vEDS substitutions within a high-affinity integrin α2β1-binding motif, GROGER. We used these peptides to investigate, at atomic-level resolution, how these amino acid substitutions affect the collagen III-integrin α2β1 interaction. Using a multitiered approach combining biological adhesion assays, CD, NMR, and molecular dynamics (MD) simulations, we found that these substitutions differentially impede human mesenchymal stem cell spreading and integrin α2-inserted (α2I) domain binding to the CMPs and were associated with triple-helix destabilization. Although an Ala substitution locally destabilized hydrogen bonding and enhanced mobility, it did not significantly reduce the CMP-integrin interactions. MD simulations suggested that bulkier Gly → Xaa substitutions differentially disrupt the CMP-α2I interaction. The Gly → Arg substitution destabilized CMP-α2I side-chain interactions, and the Gly → Val change broke the essential Mg2+ coordination. The relationship between the loss of functional binding and the type of vEDS substitution provides a foundation for developing potential therapies for managing collagen disorders.

Collagen-binding proteins: insights from the Collagen Toolkits.

The Collagen Toolkits are libraries of 56 and 57 triple-helical synthetic peptides spanning the length of the collagen II and collagen III helices. These have been used in solid-phase binding assays to locate sites where collagen receptors and extracellular matrix components bind to collagens. Truncation and substitution allowed exact binding sites to be identified, and corresponding minimal peptides to be synthesised for use in structural and functional studies. 170 sites where over 30 proteins bind to collagen II have been mapped, providing firm conclusions about the amino acid distribution within such binding sites. Protein binding to collagen II is not random, but displays a periodicity of approximately 28 nm, with several prominent nodes where multiple proteins bind. Notably, the vicinity of the collagenase-cleavage site in Toolkit peptide II-44 is highly promiscuous, binding over 20 different proteins. This may reflect either the diverse chemistry of that locus or its diverse function, together with the interplay between regulatory binding partners. Peptides derived from Toolkit studies have been used to determine atomic level resolution of interactions between collagen and several of its binding partners and are finding practical application in tissue engineering.

The Influence of the Extracellular Matrix in Inflammation: Findings from the SPARC-Null Mouse.

Matricellular proteins are secreted proteins that, among other functions, can contribute to extracellular matrix (ECM) assembly including modulation of cell:ECM interactions. Recent discoveries have indicated a fundamental role for the ECM in the regulation of inflammatory responses including cell extravasation and recruitment, immune cell differentiation, polarization, activation, and retention in tissues. Secreted protein acidic and rich in cysteine (SPARC) is a matricellular collagen-binding protein implicated in fibrillar collagen assembly in the ECM of connective tissue as well as in basal lamina organization. Functions of SPARC in modulating cell adhesion events are also reported. Studies of phenotypic responses observed in SPARC-null mice to a variety of injury models have yielded interesting insight into the functional importance of SPARC production and aberrations in ECM structure that occur in the absence of SPARC that influence immune cell behavior and inflammatory pathways. In this review, we will discuss several examples from different tissues in which SPARC-null mice exhibited an inflammatory response distinct from those of SPARC expressing mice and provide insight into novel ECM-dependent mechanisms that influence these responses. Anat Rec, 2019. © 2019 Wiley Periodicals, Inc.

Dual role of the colonization factor CD2831 in Clostridium difficile pathogenesis

Clostridium difficile is a Gram-positive, anaerobic bacterium and the leading cause of antibiotic-associated diarrhea and pseudomembranous colitis. C. difficile modulates its transition from a motile to a sessile lifestyle through a mechanism of riboswitches regulated by cyclic diguanosine monophosphate (c-di-GMP). Previously described as a sortase substrate positively regulated by c-di-GMP, CD2831 was predicted to be a collagen-binding protein and thus potentially involved in sessility. By overexpressing CD2831 in C. difficile and heterologously expressing it on the surface of Lactococcus lactis, here we further demonstrated that CD2831 is a collagen-binding protein, able to bind to immobilized collagen types I, III and V as well as native collagen produced by human fibroblasts. We also observed that the overexpression of CD2831 raises the ability to form biofilm on abiotic surface in both C. difficile and L. lactis. Notably, we showed that CD2831 binds to the collagen-like domain of the human complement component C1q, suggesting a role in preventing complement cascade activation via the classical pathway. This functional characterization places CD2831 in the Microbial Surface Components Recognizing Adhesive Matrix Molecule (MSCRAMMs) family, a class of virulence factors with a dual role in adhesion to collagen-rich tissues and in host immune evasion by binding to human complement components.

Streptococcus mutans serotypes and collagen-binding proteins Cnm/Cbm in children with caries analysed by PCR.

Streptococcus mutans, a primary bacterium associated with dental caries, has four known clinical serotypes (c, e, fand k). Certain serotypes, the presence of multiple serotypes and strains with collagen-binding proteins (CBP, Cnm and Cbm) have been linked with systemic disease. Evaluation of S mutans serotype distribution and caries association is needed in the United States. The purpose of this study was to evaluate the prevalence of S mutans serotypes from two cohorts of African-American children in rural Alabama using three sample types (saliva, plaque and individual S mutans isolates) by PCR detection for association with caries. Detection of CBP was also performed by PCR. In total, 129 children were evaluated and overall prevalence of serotypes were: serotype c(98%), e(26%), f(7%) and k(52%). Serotype c was statistically associated with higher caries scores in older children (P<0.001) and serotype k was statistically more likely in females (P=0.004). Fourteen per cent of children had CBP. Thirteen S mutans isolates from five children tested positive for both CBP. This study is the first to report on the prevalence of S mutans serotypes in a US population using the PCR-based approach. The frequency of serotype k in this study is the highest reported in any population, illustrating the need for further study to determine the prevalence of this clinically relevant serotype in the US. This is the first study to report S mutans isolates with both Cnm and Cbm in the same strain, and further analysis is needed to determine the clinical significance of these strains.

Abstract WMP108: Brain-Oral Axis: Cnm -Positive S. mutans Infection is a Novel Risk Factor for Cerebral Bleeding

Introduction: We previously reported that oral Streptococcus mutans expressing a collagen binding protein Cnm was associated with deep cerebral microbleeds (CMBs) and intracranial hemorrhage (ICH). Approximately 20% of S. mutans strains have the cnm gene, raising the risk of cerebral bleeding. However, the positive correlation between cnm -positive S. mutans and CMBs has been shown only in cross-sectional studies and long-term effects of cnm -positive S. mutans still remain unknown. Purpose: To determine whether cnm -positive S. mutans facilitates cerebral bleeding. Methods: In our retrospective longitudinal study, 92 stroke survivors who underwent serial 3.0 T-MRI scans at intervals of more than 6 months and received analysis of oral bacteria were consecutively enrolled. Patients without oral harboring S. mutans were excluded. The cnm gene in S. mutans isolated from dental plaque was screened using PCR techniques. CMBs were illustrated by MRI T2*-weighted GRE method (TR 550 ms, TE 12 ms, flip angle 20°, slice thickness 4.0 mm). CMBs were classified into the deep, lobar, and subtentorial CMBs. After evaluation of serial MRI scans, the number of newly evoked CMBs per 6 months was compared between cnm -positive S. mutans group ( cnm+ group) and cnm -negative S. mutans group ( cnm - group). Results: Twenty-two patients were enrolled in the cnm+ group and 70 in the cnm - group (mean age±SE 69.7±2.8 vs. 69.2±1.5 p=0.56). The two groups were not different in the mean observational period (1.37±0.13 vs. 1.46±0.08 years p=0.84) or in the prevalence of vascular risk factors, including hypertension. Total and deep CMBs significantly increased in number in the cnm + group compared to the cnm - group (mean±SD per 6 months, 0.88±1.30 vs. 0.16±0.45 for total CMBs, p=0.01; 0.47±0.80 vs. 0.03±0.15 for deep CMBs, p=0.003), while lobar and subtentorial CMBs did not increase significantly (0.22±0.50 vs. 0.07±0.32 for lobar CMBs, p=0.10; 0.19±0.61 vs. 0.06±0.17 for subtentorial CMBs, p=0.24). Two (9.1%) in the cnm + group but only one (1.6%) in the cnm - group had symptomatic cerebral hemorrhage during the observational period. Conclusions: Oral cnm -positive S. mutans facilitated formation of CMBs. Brain-oral axis may be a novel therapeutic target for cerebral bleeding.

Cryptic binding sites become accessible through surface reconstruction of the type I collagen fibril

Collagen fibril interactions with cells and macromolecules in the extracellular matrix drive numerous cellular functions. Binding motifs for dozens of collagen-binding proteins have been determined on fully exposed collagen triple helical monomers. However, when the monomers are assembled into the functional collagen fibril, many binding motifs become inaccessible, and yet critical cellular processes occur. Here, we have developed an early stage atomic model of the smallest repeating unit of the type I collagen fibril at the fibril surface that provides a novel framework to address questions about these functionally necessary yet seemingly obstructed interactions. We use an integrative approach by combining molecular dynamics (MD) simulations with atomic force microscopy (AFM) experiments and show that reconstruction of the collagen monomers within the complex fibril play a critical role in collagen interactions. In particular, the fibril surface shows three major conformational changes, which allow cryptic binding sites, including an integrin motif involved in platelet aggregation, to be exposed. The observed dynamics and reconstruction of the fibril surface promote its role as a “smart fibril” to keep certain binding sites cryptic, and to allow accessibility of recognition domains when appropriate.

CovR and VicRKX Regulate Transcription of the Collagen Binding Protein Cnm of Streptococcus mutans.

Cnm is a surface-associated protein present in a subset of Streptococcus mutans strains that mediates binding to extracellular matrices, intracellular invasion, and virulence. Here, we showed that cnm transcription is controlled by the global regulators CovR and VicRKX. In silico analysis identified multiple putative CovR- and VicR-binding motifs in the regulatory region of cnm as well as in the downstream gene pgfS, which is associated with the posttranslational modification of Cnm. Electrophoretic mobility shift assays revealed that CovR and VicR specifically and independently bind to the cnm and pgfS promoter regions. Quantitative real-time PCR and Western blot analyses of ΔcovR and ΔvicK strains as well as of a strain overexpressing vicRKX revealed that CovR functions as a positive regulator of cnm, whereas VicRKX acts as a negative regulator. In agreement with the role of VicRKX as a repressor, the ΔvicK strain showed enhanced binding to collagen and laminin and higher intracellular invasion rates. Overexpression of vicRKX was associated with decreased rates of intracellular invasion but did not affect collagen or lamin binding activities, suggesting that this system controls additional genes involved in binding to these extracellular matrix proteins. As expected, based on the role of CovR in cnm regulation, the ΔcovR strain showed decreased intracellular invasion rates, but, unexpectedly collagen and laminin binding activities were increased in this mutant strain. Collectively, the results presented here expand the repertoire of virulence-related genes regulated by CovR and VicRKX to include the core gene pgfS and the noncore gene cnmIMPORTANCEStreptococcus mutans is a major pathogen associated with dental caries and also implicated in systemic infections, in particular, infective endocarditis. The Cnm adhesin of S. mutans is an important virulence factor associated with systemic infections and caries severity. Despite its role in virulence, the regulatory mechanisms governing cnm expression are poorly understood. Here, we describe the identification of two independent regulatory systems controlling the transcription of cnm and the downstream pgfS-pgfM1-pgfE-pgfM2 operon. A better understanding of the mechanisms controlling expression of virulence factors like Cnm can facilitate the development of new strategies to treat bacterial infections.

Structure of ScpC, a virulence protease from Streptococcus pyogenes, reveals the functional domains and maturation mechanism.

Group A Streptococcus (GAS; Streptococcus pyogenes) causes a wide range of infections, including pharyngitis, impetigo, and necrotizing fasciitis, and results in over half a million deaths annually. GAS ScpC (SpyCEP), a 180-kDa surface-exposed, subtilisin-like serine protease, acts as an essential virulence factor that helps S. pyogenes evade the innate immune response by cleaving and inactivating C-X-C chemokines. ScpC is thus a key candidate for the development of a vaccine against GAS and other pathogenic streptococcal species. Here, we report the crystal structures of full-length ScpC wild-type, the inactive mutant, and the ScpC-AEBSF inhibitor complex. We show ScpC to be a multi-domain, modular protein consisting of nine structural domains, of which the first five constitute the PR + A region required for catalytic activity. The four unique C-terminal domains of this protein are similar to collagen-binding and pilin proteins, suggesting an additional role for ScpC as an adhesin that might mediate the attachment of S. pyogenes to various host tissues. The Cat domain of ScpC is similar to subtilisin-like proteases with significant difference to dictate its specificity toward C-X-C chemokines. We further show that ScpC does not undergo structural rearrangement upon maturation. In the ScpC-inhibitor complex, the bound inhibitor breaks the hydrogen bond between active-site residues, which is essential for catalysis. Guided by our structure, we designed various epitopes and raised antibodies capable of neutralizing ScpC activity. Collectively, our results demonstrate the structure, maturation process, inhibition, and substrate recognition of GAS ScpC, and reveal the presence of functional domains at the C-terminal region.

Expression of Adhesive Pili and the Collagen-Binding Adhesin Ace Is Activated by ArgR Family Transcription Factors in Enterococcus faecalis.

It was shown previously that the disruption of the ahrC gene encoding a predicted ArgR family transcription factor results in a severe defect in biofilm formation in vitro, as well as a significant attenuation of virulence of Enterococcus faecalis strain OG1RF in multiple experimental infection models. Using transcriptome sequencing (RNA-seq), we observed ahrC-dependent changes in the expression of more than 20 genes. AhrC-repressed genes included predicted determinants of arginine catabolism and several other metabolic genes and predicted transporters, while AhrC-activated genes included determinants involved in the production of surface protein adhesins. Most notably, the structural and regulatory genes of the ebp locus encoding adhesive pili were positively regulated, as well as the ace gene, encoding a collagen-binding adhesin. Using lacZ transcription reporter fusions, we determined that ahrC and a second argR transcription factor gene, argR2, both function to activate the expression of ebpR, which directly activates the transcription of the pilus structural genes. Our data suggest that in the wild-type E. faecalis, the low levels of EbpR limit the expression of pili and that biofilm biomass is also limited by the amount of pili expressed by the bacteria. The expression of ace is similarly enhanced by AhrC and ArgR2, but ace expression is not dependent on EbpR. Our results demonstrate the existence of novel regulatory cascades controlled by a pair of ArgR family transcription factors that might function as a heteromeric protein complex.IMPORTANCE Cell surface adhesins play critical roles in the formation of biofilms, host colonization, and the pathogenesis of opportunistic infections by Enterococcus faecalis Here, we present new results showing that the expression of two major enterococcal surface adhesins, ebp pili, and the collagen-binding protein Ace is positively regulated at the transcription level by two argR family transcription factors, AhrC and ArgR2. In the case of pili, the direct target of regulation is the ebpR gene, previously shown to activate the transcription of the pilus structural genes, while the activation of ace transcription appears to be directly impacted by the two ArgR proteins. These transcription factors may represent new targets for blocking enterococcal infections.

Abstract A031: Androgen deprivation therapy-induced TGFBI signaling promotes EMT and bone metastasis of prostate cancer

Abstract Metastatic progression in patients with prostate cancer is common despite pharmacologic inhibition of androgen receptor signaling. This drug resistance is associated with increased signaling through the transforming growth factor-β (TGF-β) signaling pathway. We found the type I/II/IV collagen-binding protein transforming growth factor-β (TGF-β)-induced (TGFBI) is an important factor in the epithelial-to-mesenchymal transition (EMT) and malignant progression of prostate cancer. We identified that an androgen-responsive gene, SPDEF, navigates between AR and TGFβ signaling during prostate cancer progression to metastasis though a physical interaction with the promoter region of the TGFBI gene. We show that loss of AR-regulated SPDEF induces TGFBI expression in prostate cancer cells, leading to drastic and aggressive physiologic changes. Furthermore, we confirmed the negative correlation between SPDEF and TGFβ singling in prostate cancer patients and demonstrated that ADT can reduce SPDEF and increase TGFβ signaling. Our results support an inhibitory role of the AR on TGFβ signaling through SPDEF-mediated suppression of TGFBI, and that disruption of this pathway promotes metastatic progression in prostate cancer. Citation Format: Yen-Nien Liu, Wei-Yu Chen, Yuan-Chin Tsai, Hsiu-Lien Yeh, Florent Suau, Jiaoti Huang. Androgen deprivation therapy-induced TGFBI signaling promotes EMT and bone metastasis of prostate cancer [abstract]. In: Proceedings of the AACR Special Conference: Prostate Cancer: Advances in Basic, Translational, and Clinical Research; 2017 Dec 2-5; Orlando, Florida. Philadelphia (PA): AACR; Cancer Res 2018;78(16 Suppl):Abstract nr A031.

Collagen-binding Streptococcus Mutans Tied to Cerebral Microbleeds and Intracerebral Hemorrhage

Genome-wide association and candidate gene studies have identified COL4A1 and COL4A2 as risk genes for intracerebral hemorrhage (ICH), suggesting that the disrupted collagen architecture could be a contributory factor in disease onset. Environmental factors that disrupt the vascular collagen architecture may therefore bring about gene–environmental interactions. Certain oral strains of Streptococcus mutans expressing Cnm, a collagen-binding protein, have been found to be responsible for ICH in a preclinical study. In support of this finding, a population-based study showed a close association between Cnm-positive Streptococcus mutans with cerebral microbleeds, a precursor of ICH, and a hospital-based study between such bacteria with cerebral microbleeds and ICH. Taken together, these findings suggest that Cnm-positive Streptococcus mutans serve as an important environmental factor in ICH.

Streptococcus mutans with Collagen-Binding Protein: From Oral Cavity to Brain

Streptococcus mutans with Collagen-Binding Protein: From Oral Cavity to Brain

In Reply to “Streptococcus mutans with Collagen-Binding Protein: From Oral Cavity to Brain”

In Reply to “Streptococcus mutans with Collagen-Binding Protein: From Oral Cavity to Brain”

CT imaging of myocardial scar burden with CNA35-conjugated gold nanoparticles

Management of patients suffering from myocardial infarction (MI) is based on the extent of coronary artery disease and myocardial scar burden. We have developed a potentially clinically-useful X-ray molecular imaging contrast agent based on gold nanoparticle (AuNPs) functionalized with collagen-binding adhesion protein 35 (CNA35) with the capabilities of achieving prolonged blood pool enhancement for vascular imaging of the coronary arteries and specific targeting of collagen within myocardial scar. At a concentration of ~ 45 mg Au/ml, AuNPs maintained a stable blood pool enhancement at 142–160 HU within an hour of intravenous administration. At 6 hours, specific signal enhancement was detected in the myocardium scar in rats injected with CNA35-AuNPs, but not with control AuNPs or in control animals. In conclusion, CNA35-AuNPs may be considered as a CT contrast agent for both vascular imaging of coronary artery disease and molecular imaging of myocardial scar in the heart.

The chaperone protein HSP47: a platelet collagen binding protein that contributes to thrombosis and hemostasis

Essentials Heat shock protein 47 (HSP47), a collagen specific chaperone is present on the platelet surface.Collagen mediated platelet function was reduced following blockade or deletion of HSP47.GPVI receptor regulated signalling was reduced in HSP47 deficient platelets.Platelet HSP47 tethers to exposed collagen thus modulating thrombosis and hemostasis. SummaryObjectiveHeat shock protein 47 (HSP47) is an intracellular chaperone protein that is vital for collagen biosynthesis in collagen secreting cells. This protein has also been shown to be present on the surface of platelets. Given the importance of collagen and its interactions with platelets in triggering hemostasis and thrombosis, in this study we sought to characterize the role of HSP47 in these cells.Methods and ResultsThe deletion of HSP47 in mouse platelets or its inhibition in human platelets reduced their function in response to collagen and the GPVI agonist (CRP‐XL), but responses to thrombin were unaltered. In the absence of functional HSP47, the interaction of collagen with platelets was reduced, and this was associated with reduced GPVI‐collagen binding, signalling and platelet activation. Thrombus formation on collagen, under arterial flow conditions, was also decreased following the inhibition or deletion of HSP47, in the presence or absence of eptifibatide, consistent with a role for HSP47 in enhancing platelet adhesion to collagen. Platelet adhesion under flow to von Willebrand factor was unaltered following HSP47 inhibition. Laser‐induced thrombosis in cremaster muscle arterioles was reduced and bleeding time was prolonged in HSP47‐deficient mice or following inhibition of HSP47.ConclusionsOur study demonstrates the presence of HSP47 on the platelet surface, where it interacts with collagen, stabilizes platelet adhesion and increases collagen‐mediated signalling and therefore thrombus formation and hemostasis.

Campylobacter rectus in the Oral Cavity Correlates with Proteinuria in Immunoglobulin A Nephropathy Patients

Background: Periodontitis-related pathogens, such as Campylobacter or Treponema species, have recently been shown to be associated with immunoglobulin A nephropathy (IgAN). Some strains of Streptococcus mutans, a major pathogen of dental caries, harbour the cnm gene that encodes a collagen-binding protein (Cnm). This has also been demonstrated to be associated with urinary protein levels in IgAN patients. Objectives: The purpose of the present study was to analyse the association of IgAN with C. rectus, Treponema denticola and cnm-positive S. mutans in the oral cavity of humans. Methods: The presence of C. rectus, T. denticola and cnm-positive S. mutans strains in saliva samples of 117 IgAN patients and 56 healthy controls was evaluated by PCR, and the subjects’ clinical parameters were analysed. Results: C. rectus was significantly more prevalent in the IgAN group than in the control group (p < 0.05). The C. rectus-positive group was significantly associated with proteinuria in the IgAN group (p < 0.05). In addition, the C. rectus-positive and cnm-positive S. mutans group was shown to be more closely associated with urinary protein levels than the other groups (p < 0.0083). Conclusion: Our results suggest that harbouring C. rectus in the oral cavity could be associated with proteinuria in IgAN patients.