Browsing by Subject "Metalloproteinases"

Now showing 1 - 5 of 5
  • Thumbnail Image
    Publication
    Open Access
    Interplay between metalloproteinases and cell signalling in blood brain barrier integrity
    (Universidad de Murcia. Departamento de Biología Celular e Histología, 2018) Pla Navarro, Irene; Bevan, Damon; Hajihosseini, Mohammad K.; Lee, Martin; Gavrilovic, Jelena
    The Blood-Brain Barrier (BBB) is a highly specialised interface separating the Central Nervous System (CNS) from circulating blood. Dysregulation of the BBB is a key early event in pathological conditions such as inflammation, in which the entry of activated leukocytes into the CNS is facilitated by BBB breakdown. The metzincin family of metalloproteinases (MPs) is one of the major contributors to BBB permeability as they cleave endothelial cell-cell contacts and underlying basal lamina components. However, the mechanisms by which MPs regulate BBB integrity has not yet been fully elucidated. The aim of this review is to provide an overview of pathways by which MPs could regulate the BBB in the context of neuroinflammation.
  • Thumbnail Image
    Publication
    Open Access
    Matrix metalloproteinase-1 (MMP-1) and (MMP-8) gene polymorphisms promote increase and remodeling of the collagen III and V in posterior tibial tendinopathy
    (Universidad de Murcia. Departamento de Biología Celular e Histología, 2018) Diniz Fernandes, Tulio; Godoy Santos, Alexandre Leme; Santos, Maria Cristina; Pontin, Pedro; Alves Pereira, Caio Augusto; Justi Jardim, Yuri; Pereira Velosa, Ana Paula; Maffulli, Nicola; Teodoro, Walcy Rosolia; Capelozzi, Vera Luiza
    Posterior tibial tendinopathy (PTT) can lead to acquired flatfoot in adults. Many patients develop PTT without any identifiable risk factors. Molecular changes in extracellular matrix (ECM) and matrix metalloproteinase (MMP) polymorphism may influence the risk of developing PTT. We aim to investigate the association between matrix metalloproteinase-1 (MMP1) and (MMP-8) gene polymorphisms with changes in collagen I, III and V in PTT. A case-control study with 22 patients and 5 controls was performed. The MMP-1 (2G/2G) and MMP-8 (T/T) genotypes were determined by PCR-restriction fragment length polymorphism. Tendon specimens were evaluated by a histologic semiquantitative score, immunofluorescence and histomorphometry for collagen I, III and V. Tendon specimens from PTT demonstrated marked distortion of the architecture with necrosis, large basophilic areas with disruption of the normal linear orientation of collagen bundles, infiltration of inflammatory cells, dystrophic calcification and ossification. Under immunofluorescence, PTT tendon specimens showed weak green fluorescence and diffuse distribution of collagen I fibers, but strong fluorescence of collagen III and V. The collagen I fibers were significantly decreased whereas an increase of collagen III and V were found in PTT compared to control groups. In addition, PTT group presented a significant association with MMP-1 and MMP-8 gene polymorphisms. Patients with PTT matrix metalloproteinase-1 (MMP-1) and (MMP-8) gene polymorphisms presented an increase of the collagen III and V ratio, suggesting that the higher proportion in degenerated tendons could contribute to a decrease in the mechanical resistance of the tissue. Still, functional and association studies are needed to elucidate evident roles of MMPs in PTT.
  • Thumbnail Image
    Publication
    Open Access
    Molecular evidence of tissue remodeling in an animal model of heart failure
    (Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2019) Silva Nascimento, Lais; Martins Tedesco, Larissa; Silva Araujo, Natiele; Marinho Priviero, Fernanda Bruschi; Claudino, Mario Angelo; Gonçalves Priolli, Denise; Rocha, Thalita
    Heart failure (HF) is the final common pathway of many cardiovascular diseases. Metalloproteinases and their inhibitors, such as MMP9 and TIMP-1, assist in maintaining the extracellular matrix, leading to tissue remodeling observed after HF. Previous studies have shown that L-Arginine (LA) appears to have beneficial effects for the treatment of HF, contributing to vasodilation, the reestablishment of the endothelial function and an increase in muscle contractile force. This study analyzed heart tissue remodeling in an animal model of HF induced by aortocaval fistula (ACF) and submitted to LA treatment. After 4 weeks of ACF, animals were treated with LA for 4 weeks (SHAM-LA, HF-LA) or for 8-12 weeks with saline (SHAM, HF8, HF12). Rats were euthanized and the hearts removed for histological processing. The samples were stained with Hematoxylin-Eosin (HE), Masson’s Thichome (MT), or submitted to immunohistochemistry (IHC) for MMP9 and TIMP-1. Light microscopy analysis showed cardiac striated muscle without fibrosis in all experimental groups. Immunostaining of MMP9 and TIMP-1 were positive for all experimental groups. LA administration significatively reduced MMP9 content after HF. These data indicate molecular changes in metalloproteinases expression prior to tissue remodeling and point out LA as an adjuvant therapy to pharmacological treatment of patients with HF.
  • Thumbnail Image
    Publication
    Open Access
    RECK, a novel matrix metalloproteinase regulator
    (Murcia : F. Hernández, 2008) Meng, N.; Li, Y.; Zhang, H.; Sun, X-F.
    Extracellular matrix (ECM) macromolecules are important for creating the cellular environments required during development and morphogenesis of tissues. Matrix metalloproteinases (MMPs) are a family of Zn-dependent endopeptidases that collectively are capable of cleaving virtually all ECM substrates, and play an important role in some physiological and pathological processes. MMP activity can be inhibited by some natural and artificial inhibitors. A newly found membrane-anchored regulator of MMPs, the reversioninducing- cysteine-rich protein with kazal motifs (RECK), is downregulated when the cells undergo a process of malignant transformation, and is currently the subject of considerable research activity because of its specific structure and function. In this review, we have chosen to concentrate our efforts on the structure, function, regulation, and future prospect of RECK in order to provide a new target for prevention and treatment of tumours.
  • Thumbnail Image
    Publication
    Open Access
    Remodelling of collagen fibres in the placentas of women with venous insufficiency during pregnancy
    (Universidad de Murcia. Departamento de Biología Celular e Histología, 2018) Ortega, Miguel A.; Asúnsolo, Ángel; Álvarez Rocha, María J.; Romero, Beatriz; De León-Luis, Juan; Álvarez Mon, Melchor; Buján, Julia; García Honduvilla, Natalio
    Haemodynamic changes produced during pregnancy lead to elevated venous pressure in the legs and an increased resting consumption of oxygen. These events can cause varicose veins, or venous insufficiency (VI), which by creating an environment of hypoxia could affect the structure and function of the placental barrier. This study assesses the remodelling state of the placental villi by examining differences in collagens with a known role in villus structure and in placental barrier permeability between patients with and without VI. Samples of 67 placentas from women with VI (n=24) and without VI (n=43) during their pregnancy were processed for gene and protein expression analysis of COL-I, COL-III, MMP-2 and MMP-9 by RT-qPCR and immunohistochemistry. While no differences in COL-I expression levels were detected in the samples from women with and without VI, significant differences did emerge in both gene and protein expression levels of COL-III. Importantly, COL-I/III ratios were reduced in the VI group compared to controls. MMP-2 activity was similar in the two groups while MMP-9 levels were significantly elevated in VI with greatest expression differences observed at the level of the decidual cells. Mothers who developed VI during pregnancy showed significantly higher COL-III and MMP-9 levels consistent with a state of remodelling of the placental villi.