Browsing by Subject "Collagen Type I"

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Open Access
Histoarchitecture of the fibrillary matrix of human fetal posterior tibial tendons.
(Scientific reports, 2022-10) Macedo, Rodrigo Sousa; Teodoro, Walcy Rosolia; Capellozzi, Vera Luiza; Rosemberg, Dov Lagus; Sposeto, Rafael Barban; de Cesar Netto, Cesar; Deland, Jonathan T; Maffulli, Nicola; Ellis, Scott J; Godoy-Santos, Alexandre Leme
Adult tendons are highly differentiated. In mature individuals, tendon healing after an injury occurs through fibrotic tissue formation. Understanding the intrinsic reparative properties of fetal tendons would help to understand the maturation tissue process and tendon tissue repair. The present study evaluated the evolution of histoarchitecture, cellularity and the distribution of collagens I, III and V in the posterior tibial tendon in human fetuses at different gestational ages. Morphological profiles were assessed in nine fresh spontaneously aborted fetuses (Group I: five fetuses aged between 22 and 28 weeks of gestation; Group II: four fetuses aged between 32 and 38 weeks of gestation), characterized by a combination of histology, fluorescence and immunohistochemistry. In Group I, the posterior tibial tendon showed statistically significant greater cellularity and presence of collagen III and V than in Group II tendon, which showed a predominance of collagenous I and a better organization of the extracellular matrix compared with Group I tendons. In addition, a statistically significant higher rate of CD90, a marker of mesenchymal cells, was found in Group I tendons. In fetuses with gestational age between 22 and 28 weeks, the posterior tibialis tendons showed a thin and disorganized fibrillar structure, with an increase in collagen III and V fibers and mesenchymal cells. In the posterior tibialis tendons of fetuses with gestational age between 32 and 38 weeks, the fibrillar structure was thicker with a statistically significant increase in type I collagen and decreased cellularity.
Open Access
Interleukin-13 induces collagen type-1 expression through matrix metalloproteinase-2 and transforming growth factor-β1 in airway fibroblasts in asthma.
(The European respiratory journal, 2014-02) Firszt, Rafael; Francisco, Dave; Church, Tony D; Thomas, Joseph M; Ingram, Jennifer L; Kraft, Monica
Airway remodelling is a feature of asthma that contributes to loss of lung function. One of the central components of airway remodelling is subepithelial fibrosis. Interleukin (IL)-13 is a key T-helper 2 cytokine and is believed to be the central mediator of allergic asthma including remodelling, but the mechanism driving the latter has not been elucidated in human asthma. We hypothesised that IL-13 stimulates collagen type-1 production by the airway fibroblast in a matrix metalloproteinase (MMP)- and transforming growth factor (TGF)-β1-dependent manner in human asthma as compared to healthy controls. Fibroblasts were cultured from endobronchial biopsies in 14 subjects with mild asthma and 13 normal controls that underwent bronchoscopy. Airway fibroblasts were treated with various mediators including IL-13 and specific MMP-inhibitors. IL-13 significantly stimulated collagen type-1 production in asthma compared to normal controls. Inhibitors of MMP-2 significantly attenuated collagen production in asthma but had no effect in normal controls. IL-13 significantly increased total and active forms of TGF-β1, and this activation was blocked using an MMP-2 inhibitor. IL-13 activated endogenous MMP-2 in asthma patients as compared to normal controls. In an ex vivo model, IL-13 potentiates airway remodelling through a mechanism involving TGF-β1 and MMP-2. These effects provide insights into the mechanism involved in IL-13-directed airway remodelling in asthma.
Open Access
Systemic EP4 Inhibition Increases Adhesion Formation in a Murine Model of Flexor Tendon Repair.
(PloS one, 2015-01) Geary, Michael B; Orner, Caitlin A; Bawany, Fatima; Awad, Hani A; Hammert, Warren C; O'Keefe, Regis J; Loiselle, Alayna E
Flexor tendon injuries are a common clinical problem, and repairs are frequently complicated by post-operative adhesions forming between the tendon and surrounding soft tissue. Prostaglandin E2 and the EP4 receptor have been implicated in this process following tendon injury; thus, we hypothesized that inhibiting EP4 after tendon injury would attenuate adhesion formation. A model of flexor tendon laceration and repair was utilized in C57BL/6J female mice to evaluate the effects of EP4 inhibition on adhesion formation and matrix deposition during flexor tendon repair. Systemic EP4 antagonist or vehicle control was given by intraperitoneal injection during the late proliferative phase of healing, and outcomes were analyzed for range of motion, biomechanics, histology, and genetic changes. Repairs treated with an EP4 antagonist demonstrated significant decreases in range of motion with increased resistance to gliding within the first three weeks after injury, suggesting greater adhesion formation. Histologic analysis of the repair site revealed a more robust granulation zone in the EP4 antagonist treated repairs, with early polarization for type III collagen by picrosirius red staining, findings consistent with functional outcomes. RT-PCR analysis demonstrated accelerated peaks in F4/80 and type III collagen (Col3a1) expression in the antagonist group, along with decreases in type I collagen (Col1a1). Mmp9 expression was significantly increased after discontinuing the antagonist, consistent with its role in mediating adhesion formation. Mmp2, which contributes to repair site remodeling, increases steadily between 10 and 28 days post-repair in the EP4 antagonist group, consistent with the increased matrix and granulation zones requiring remodeling in these repairs. These findings suggest that systemic EP4 antagonism leads to increased adhesion formation and matrix deposition during flexor tendon healing. Counter to our hypothesis that EP4 antagonism would improve the healing phenotype, these results highlight the complex role of EP4 signaling during tendon repair.