Capillary morphogenesis protein-2 (CMG2) functions as an anthrax toxin receptor that plays an essential role in anthrax pathogenesis. Although mutations in CMG2 have been identified to cause two human autosomal recessive disorders, Juvenile Hyaline Fibromatosis and Infantile Systemic Hyalinosis, both characterized by excess hyaline material deposition in connective tissues, the ...

Diastrophic dysplasia (DTD) is an incurable recessive chondrodysplasia caused by mutations in SLC26A2 transporter responsible for sulfate uptake by chondrocytes. The mutations cause undersulfation of glycosaminoglycans in cartilage. Studies of dtd mice with a knock-in Slc26a2 mutation showed an unusual progression of the disorder: net undersulfation is mild and normalizing ...

OBJECTIVE: To investigate the mechanisms by which chronic tobacco smoking promotes intervertebral disc degeneration (IDD) and vertebral degeneration in mice. METHODS: Three months old C57BL/6 mice were exposed to tobacco smoke by direct inhalation (5 cigarettes/day, 5 days/week for 6 months) to model long-term smoking in humans. Total disc proteoglycan ...

Markers of fetal inflammatory response syndrome (FIRS) can influence the morphologic alterations in liver of autopsied neonates. The IL-6, TNF-α, and C-reactive protein (CRP) expression in liver fragments were marked by immunohistochemistry and the intensity of steatosis, percentage of fibrosis, and the number of foci of extramedullary erythropoiesis were evaluated. ...

OBJECTIVE: To analyse the function of nucleotide pyrophosphatase phosphodiesterase (NPP1), a member of the pyrophosphate pathway, in osteoarthritis (OA).METHODS: mRNA expression of NPP1, ANK ankylosing protein and tissue non-specific alkaline phosphatase was assessed by quantitative PCR. NPP1 protein levels were analysed in mouse and human cartilage samples. Bone metabolism was ...

Heat shock protein 47 (HSP47), a collagen-specific molecular chaperone, is essential for the biosynthesis and secretion of collagen and is expressed in the fibrotic peritoneum. In the present study, we evaluated the efficacy of HSP47 small interfering RNA (siRNA) to suppress the development of peritoneal fibrosis induced by chlorhexidine gluconate ...

Structural extracellular matrix molecules (ECM) gain increasing attention as scaffolds for cartilage tissue engineering due to their natural role as a growth factor repository. We recently observed that a collagen-type I/III matrix (Col-I/III), human recombinant TGF-β protein, and fibrin glue (FG) combined to a biphasic construct provided sufficient long-term TGF-β ...

ABSTRACT Idiopathic pulmonary fibrosis (IPF) is characterized by interstitial lung infiltrates, dyspnea, and progressive respiratory failure. Reports linking telomerase mutations to familial interstitial pneumonia (FIP) suggest that telomerase activity and telomere length maintenance are important in disease pathogenesis. To investigate the role of telomerase in lung fibrotic remodeling, intratracheal bleomycin ...

Background  Keloids are benign dermal tumors characterized by fibroblastic proliferation and excessive accumulation of collagen. Oxymatrine (OMT) is an alkaloid extracted from the Chinese herb Sophora japonica with capacities of anti-fibrosis. Objective  To evaluate the effects of OMT on collagen production and to explore its mechanisms. Methods  OMT was applied ...

Atopic dermatitis (AD) skin lesions exhibit epidermal and dermal thickening, eosinophil infiltration, and increased levels of the cysteinyl leukotriene (cys-LT) leukotriene C(4) (LTC(4)). Epicutaneous sensitization with ovalbumin of WT mice but not ΔdblGATA mice, the latter of which lack eosinophils, caused skin thickening, collagen deposition, and increased mRNA expression of ...

Mutations in hemochromatosis protein (HFE) or transferrin receptor 2 (TFR2) cause hereditary hemochromatosis (HH) by impeding production of the liver iron regulatory hormone, hepcidin (HAMP). This study examined the effects of disruption of Hfe or Tfr2, either alone or together, on liver iron loading and injury in mouse models of ...

Heat shock protein 47 kDa (Hsp47) is considered as a molecular chaperone essential for the correct folding of type I and type IV procollagen in the ER. However, the function of Hsp47 for other types of procollagen and its importance for chondrogenesis have never been elucidated. To examine the function ...

Non-invasive diagnosis of atherosclerosis via single biomarkers has been attempted but remains elusive. However, a previous polymarker or pattern approach of urine polypeptides in humans reflected coronary artery disease with high accuracy. The aim of the current study is to use urine proteomics in ApoE-/- mice to discover proteins with ...

BACKGROUND: -Arrhythmogenic ventricular remodeling is hallmarked by both reduced gap junction expression and increased collagen deposition. We hypothesized that reduced Cx43 expression is responsible for enhanced fibrosis in the remodeled heart, resulting in an arrhythmogenic substrate. Therefore, we investigated the effect of normal or reduced Cx43 expression on the formation ...

BACKGROUND: Dry skin causes pruritus and discomfort in patients with xerosis and atopic dermatitis. General treatment for skin dryness involves the topical application of an emollient. However, more effective, simpler therapies are desired. Collagen tripeptide (CTP) is a highly purified, non-antigenic, low-allergenic collagen fraction that is known to have various ...

OBJECTIVE: We assessed the role of Ank in the maintenance of postnatal articular cartilage using the ank/ank mouse (mice homozygous for progressive ankylosis). METHODS: We analyzed ank/ank mice and wild-type littermates (8, 12, and 18 weeks old). Sections from decalcified, paraffin-embedded joints were stained with hematoxylin and eosin. Articular chondrocyte ...

Background: Increased myocardial extracellular matrix collagen represents an important structural milestone during the development of left ventricular (LV) pressure overload (PO); however, the proteolytic pathways that contribute to this process are not fully understood. This study tested the hypothesis that membrane type-1 matrix metalloproteinase (MT1-MMP) is directly induced at the ...

OBJECTIVE.: Calcineurin-binding protein 1 (Cabin1) regulates calcineurin phosphatase activity as well as the activation, apoptosis, and inflammatory responses of fibroblast-like synoviocytes (FLSs), which actively participate in the chronic inflammatory responses in rheumatoid arthritis (RA). However, the mechanism of action of Cabin1 in FLS apoptosis is not clear. The aim of ...

In this study we investigated the effects of genetic deletion of the Angiotensin-(1-7) receptor Mas or the Angiotensin II receptor AT(2) on the expression of specific extracellular matrix (ECM) proteins in atria, right ventricles and atrioventricular (AV) valves of neonatal and adult mice. Quantification of collagen types I, III and ...

Fibrosis of the liver and its end-stage, cirrhosis, represent major health problems worldwide. In these fibrotic conditions activated fibroblasts and hepatic stellate cells display a net deposition of collagen. This collagen deposition is a major factor leading to liver dysfunction, thus making it crucially important to understand both the collagen ...

Previously, the authors demonstrated that the lack of the P2X(7) receptor impairs epithelial wound healing and stromal collagen organization in the cornea. The goal here is to characterize specific effects of the P2X(7) receptor on components of the corneal stroma extracellular matrix. Unwounded corneas from P2X(7) knockout mice (P2X(7) (-/-)) ...

The aim of this study was to examine the proliferative ability of dibutyryl chitin (DBC) on scratch wounds in HaCaT keratinocytes and to evaluate the effect of nanoporous non-woven mat (DBCNFM) on skin wound healing in hairless mice using the advantages of DBCNFM, such as high porosity and high surface ...

Mutation or loss of collagen VI has been linked to a variety of musculoskeletal abnormalities, particularly muscular dystrophies, tissue ossification and/or fibrosis, and hip osteoarthritis. However, the role of collagen VI in bone and cartilage structure and function in the knee is unknown. In this study, we examined the role ...

Rheumatoid arthritis (RA) is an inflammatory articular disease with cartilage and bone damage due to hyperplasic synoviocyte invasion and subsequent matrix protease digestion. Although monoclonal antibodies against tumor necrosis factor alpha (TNFα) have been approved for clinical use in patients with RA, desired therapeutic regimens suitable for non-responders are still ...

Extracellular superoxide dismutase (SOD3), an enzyme mediating dismutation of superoxide into hydrogen peroxide, has been shown to reduce inflammation by inhibiting macrophage migration into injured tissues. In inflamed tissues, superoxide is produced by the phagocytic NOX2 complex, which consists of the catalytic subunit NOX2 and several regulatory subunits (e.g., NCF1). ...

Anthrax Toxin Receptor proteins function as receptors for anthrax toxin, however physiological activity remains unclear. To evaluate the biological role of Antxr2, we generated Antxr2-/- mice. Antxr2-/- mice were viable, however Antxr2 is required for parturition in young females and for preserving fertility in older female mice. Histological analysis of ...

The purpose of this study was to compare the effectiveness of moxibustion (MOX) treatment at the GV4 and CV12 acupoints, and to determine the correlations between MOX treatment and interleukin (IL)-6 and corticosterone levels in a collagen-induced arthritis (CIA) mouse model. CIA mice were immunized twice intradermally over a 3-week ...

Objectives  We aimed to determine the anti-arthritis effect and its mechanism of a combination of herbal extracts from Trachelospermi caulis (TC) and Moutan cortex radicis (MC) (TCMC). Methods  The anti-arthritis activity of TCMC was assessed using a mouse model of type II collagen-induced arthritis (CIA). Reverse transcriptase-polymerase chain reaction (RT-PCR), ...

Peña I, Junquera LM, Meana Á, García E, Aguilar C, Fresno MF. In vivo behavior of complete human oral mucosa equivalents: characterization in athymic mice. J Periodont Res 2011; 46: 214-220. © 2010 John Wiley & Sons A/S Background and Objective:  The interest in tissue engineering as a way to ...

Nitric oxide (NO) and reactive oxygen species (ROS) are key molecules in resistance to pathogens. Little is known about their role in pathogenesis of periapical lesions. To address this issue, we induced periapical lesions in mice lacking nitric oxide synthase (iNOS(-/-)) or phagocyte oxidase (PHOX(-/-)). iNOS(-/-) mice expressed higher levels ...

Cantley MD, Haynes DR, Marino V, Bartold PM: Pre-existing periodontitis exacerbates experimental arthritis in a mouse model. J Clin Periodontol 2011; doi: 10.1111/j.1600-051X.2011.01714.x. ABSTRACT: Aims: Previous studies have shown a higher incidence of alveolar bone loss in patients with rheumatoid arthritis (RA) and that patients with periodontitis are at a ...

This study sought to evaluate the effect of low-level laser treatment combined with scaling and root planing (SRP) on gingival tissue levels of TNF-alpha in subjects with periodontal disease. Eighty gingival papilla biopsy samples were obtained from 60 patients diagnosed with chronic advanced periodontitis; randomly assigned to three treatment groups ...

The aim of this study was to quantify and compare the production of transforming growth factor beta (TGF-β), interleukin (IL)-8 and IL-10 by human cultured periodontal ligament and gingival fibroblasts both obtained from the same donors challenged with lipopolysaccharide (LPS) from Porphyromonas gingivalis. Fibroblasts were exposed to 0.1-10 µg/mL of ...

Background: Earlier studies have shown an association between obesity and periodontitis, which is mediated by cytokine production. The aim of this study was to assess the role of obesity as a modifying factor on periodontal clinical parameters and upon circulating proinflammatory cytokine levels in subjects undergoing non-surgical periodontal treatment. Methods: ...

Mechanisms of progression of chronic kidney disease (CKD), a major health care burden, are poorly understood. EGFR stimulates CKD progression, but the molecular networks that mediate its biological effects remain unknown. We recently showed that the severity of renal lesions after nephron reduction varied substantially among mouse strains and required ...

The aim of the current study was to determine whether overexpression of heparin-binding epidermal growth factor-like growth factor (HB-EGF) could protect the intestines from injury after hemorrhagic shock and resuscitation in mice. Hemorrhagic shock and resuscitation was induced in HB-EGF transgenic and wild type mice. Cross-reacting material 197 (5 mg/kg) ...

Necrotizing enterocolitis (NEC) is the most common gastrointestinal emergency and the leading surgical cause of death in premature infants. We have shown that administration of exogenous heparin-binding epidermal growth factor-like growth factor (HB-EGF) in mice protects the intestines from experimental NEC. The aim of the current study was to evaluate ...

We have accumulated multiple lines of evidence supporting the ability of HB-EGF to protect the intestines from injury and to augment the healing of partial-thickness scald burns of the skin. The aim of the current study was to investigate the role of heparin-binding EGF-like growth factor (HB-EGF) in intestinal anastomotic ...

Complications arise in chronic obstructive pulmonary diseases (COPD) with excessive mucus production, especially during the exacerbation period, which contributes to airway blockage and bacterial infection. Neutrophil elastase (NE) is detected at high levels in airway secretions, and is the primary inducer of mucin production. Understanding the mechanism of NE-induced overproduction ...

While intraventricular administration of epidermal growth factor (EGF) expands the proliferation of neural stem/progenitor cells in the subventricular zone (SVZ), overexpression of brain-derived neurotrophic factor (BDNF) is particularly effective in enhancing striatal neurogenesis. We assessed the induction of striatal neurogenesis and consequent functional recovery after chronic infusion of BDNF and ...

Transforming growth factor-α (TGFα) promotes cell proliferation by binding to the epidermal growth factor receptor (EGFR). TGFα and EGFR overexpression have been reported in various human cancers. However, whether TGFα induces cancer by itself is unknown in urogenital organs. To investigate whether TGFα overexpression induces carcinogenesis in urogenital organs, we ...

The protease a disintegrin and metalloprotease (ADAM) 17 cleaves tumor necrosis factor (TNF), L-selectin, and epidermal growth factor receptor (EGF-R) ligands from the plasma membrane. ADAM17 is expressed in most tissues and is up-regulated during inflammation and cancer. ADAM17-deficient mice are not viable. Conditional ADAM17 knockout models demonstrated proinflammatory activities ...

HB-EGF, a member of the EGF family of growth factors, plays an important role in cardiac valve development by suppressing mesenchymal cell proliferation. Here, we show that HB-EGF must interact with heparan sulfate proteoglycans (HSPGs) to properly function in this process. In developing valves, HB-EGF is synthesized in endocardial cells ...

To study the role played by HB-EGF in corneal epithelial wound healing. A 2-mm corneal epithelial wound was created in keratinocyte-specific, HB-EGF-deficient mice--HB(lox/lox):K-5Cre (HB(-/-))--and the speed of wound healing was compared with that in wild-type (WT) mice. Cultured confluent mouse corneal epithelial cells (MCECs) from WT and HB(-/-) mice were ...

BACKGROUND: Overexpression of epidermal growth factor receptor (EGFR) is common in head and neck squamous cell carcinoma (HNSCC). Targeting EGFR is an effective approach to treat EGFR-positive HNSCC. However, the clinical benefits of the present EGFR-targeting agents are still limited in HNSCC patients. METHODS: Recombinant glutathione-S-transferase (GST)-EGFR fusion protein was ...

Acute respiratory distress syndrome continues to be a major source of morbidity and mortality in critically-ill patients. Heparin binding EGF-like growth factor (HB-EGF) is a biologically active protein that acts as an intestinal cytoprotective agent. We have previously demonstrated that HB-EGF protects the intestines from injury in several different animal ...

PRIMARY OBJECTIVE: Heparin-binding EGF-like growth factor (HB-EGF) protects the intestine from damage in animals. Future clinical trials of HB-EGF may involve administration of repeated doses of HB-EGF. Since HB-EGF activates EGF receptors which have been implicated in tumor development, we examined the effects of HB-EGF overexpression in the intestine. RESEARCH ...

Necrotizing enterocolitis (NEC) is the leading surgical cause of death in premature infants. We have accumulated evidence supporting a role for heparin-binding epidermal growth factor (EGF)-like growth factor (HB-EGF) in protection of the intestines from NEC. The aim of the current study was to evaluate the effect of loss-of-function of ...

We investigated whether the physiological regulation of cerebrospinal fluid (CSF) levels of tumor necrosis factor (TNF)-alpha, epidermal growth factor (EGF), and nerve growth factor (NGF) by cobalamin (Cbl) that is observed in rat and human central nervous system (CNS) is retained in the CSF of patients with multiple sclerosis (MS). ...

A visible cutaneous scar develops from the excess formation of immature collagen in response to an inflammatory reaction. This study examined the role of epidermal growth factor (EGF) in the formation of cutaneous scars. Twenty Crl:CD-1 (ICR) mice were used and 2 full-thickness skin wounds were made on the dorsum ...