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YAP/TAZ Drive Agrin-Matrix Metalloproteinase 12-Mediated Diabetic Skin Wound Healing.

Macroscopic loss of extracellular matrix can lead to chronic defects in skin wound healing, but supplementation of extracellular matrix holds promise for facilitating wound closure, particularly in diabetic wound healing. We recently showed that the extracellular matrix proteoglycan agrin accelerates cutaneous wound healing by improving mechanoperception of migrating keratinocytes and allowing them to respond to mechanical stresses through matrix metalloproteinase 12 (MMP12). RNA-sequencing analysis revealed that in addition to a disorganized extracellular matrix, agrin-depleted skin cells hav

Cadmium Toxicity on Chondrocytes and the Palliative Effects of 1α, 25-Dihydroxy Vitamin D3 in White Leghorns Chicken's Embryo.

Cadmium (Cd) can causes osteoporosis and joint swelling. However, the mechanism of Cd toxicity in chondrocytes and how to alleviate Cd poisoning to chondrocytes are still unclear. Herein, we evaluated the toxicity of Cd to chicken chondrocytes, and whether vitamin D can relieve the toxicity of Cd to chondrocytes. Primary chondrocytes were collected from knee-joint cartilage of 15-day-old chicken embryos. They were treated with (0, 1, 2, and 4) μM Cd alone, 10-8 M 1α,25-(OH)2D3 alone, or 2 μM Cd combined with 10-8 M 1α,25-(OH)2D3. We found that Cd significantly inhibited Sox9 and ACAN mRNA expr

A novel collagenase from Vibrio Alginolyticus: experimental study for Dupuytren's disease.

OBJECTIVE: Dupuytren contracture (DC) is a highly prevalent hand affection in which contracted fingers compromise hand function. It is a benign fibroproliferative condition affecting the hand palmar fascia with a deposition of excess matrix proteins in the extracellular space of the palmar aponeurosis. In particular type III over type I collagen V. Alginolyticus collagenase (CVA), is a new enzyme that is fully active on the collagen filaments and inactive on other components of the dermal extracellular matrix. The aim of this study is to evaluate the safety and effectiveness of an intra-lesion

Matrix metalloproteinase 14 modulates signal transduction and angiogenesis in the cornea.

The cornea is transparent and avascular, and retention of these characteristics is critical to maintaining vision clarity. Under normal conditions, wound healing in response to corneal injury occurs without the formation of new blood vessels; however, neovascularization may be induced during corneal wound healing when the balance between proangiogenic and antiangiogenic mediators is disrupted to favor angiogenesis. Matrix metalloproteinases (MMPs), which are key factors in extracellular matrix remodeling and angiogenesis, contribute to the maintenance of this balance, and in pathologic instanc

Enhanced expression of procollagenase in ataxia-telangiectasia and xeroderma pigmentosum fibroblasts.

Ataxia-telangiectasia and xeroderma pigmentosum are human hereditary diseases in which patients are cancer prone and demonstrate increased sensitivity to DNA damage by ionizing and ultraviolet radiation, respectively. In culture, both ataxia-telangiectasia and xeroderma pigmentosum skin fibroblasts show increased synthesis and secretion of the extracellular matrix proteins fibronectin and collagen. To determine whether these differences in protein production result from fundamental abnormalities in regulation of genes associated with cellular interactions, we compared the effects of trifluoper…

Accelerated basement membrane remodeling and serum matrix fragments as biomarkers of fibrosis in Alport syndrome.

Chronic kidney disease (CKD) is characterized by fibrosis. Alport syndrome, a common monogenic form of CKD caused by collagen type IV variants, leads to basement membrane defects and progressive fibrosis. Understanding extracellular matrix dynamics is crucial for identifying disease-specific biomarkers and optimizing therapeutic timing. We applied a discovery approach combining stable 13C-lysine metabolic labeling with proteomics, RNA sequencing, super-resolution imaging, and bioinformatics to define temporal and spatial kidney matrix dynamics in Alport mice. Transcriptomic profiling revealed

O-fucosylation of thrombospondin type 1 repeats is essential for ECM remodeling and signaling during bone development.

Many extracellular matrix (ECM) associated proteins that influence ECM properties have Thrombospondin type 1 repeats (TSRs) which are modified with O-linked fucose. The O-fucose is added in the endoplasmic reticulum to folded TSRs by the enzyme Protein O-fucosyltransferase-2 (POFUT2) and is proposed to promote efficient trafficking of substrates. The importance of this modification for function of TSR-proteins is underscored by the early embryonic lethality of mouse embryos lacking Pofut2. To overcome early lethality and investigate the impact of the Pofut2 knockout on the secretion of POFUT2

Fibroblast involvement in cardiac remodeling and repair under ischemic conditions.

Cardiac fibroblasts play a main role in the physiological turnover of the extracellular matrix, as well as its pathological remodeling. A st … tches phenotype and transdifferentiate into myofibroblast, contributing to the healing by secreting extracellular matrix proteins and collagen deposition, with subsequent cardiac remodeling and regulation of the micro-environment metabolism.

Unveiling novel biomarkers for diabetes-related complications through large-scale proteomics analysis: A FIELD sub-study.

BACKGROUND: Vascular complications of Type 2 diabetes (T2D) significantly contribute to its morbidity and mortality. Identifying robust biomarkers is critical for improving risk prediction, understanding disease mechanisms, and guiding targeted therapies. METHOD: Fasting plasma samples from a subset of 542 participants in the FIELD (Fenofibrate Intervention and Event Lowering in Diabetes) trial were subjected to mass spectrometry. Participants were divided into groups for analysis based on presence of microvascular and/or macrovascular complications, and time of its occurrence (history of at

Altered interface adhesion molecules in oral lichen planus.

OBJECTIVE: To evaluate expression of key epithelial-connective tissue interface adhesion molecules (basal keratinocyte integrins and extrace … ally more intense and appeared on more upper level cells. Staining for basement membrane-associated extracellular matrix proteins was also generally more intense, although fragmentation and gaps were typically seen. Reactions for alpha 6, beta 4, laminin 5, and collagen VII stains were particularly intense along the basement membrane. In LP, strands of laminin 5, collagen IV, …

Воздействие релаксинового экспрессии от алгинатского гель-инкапсулированного Аденовируса на реконструирование шрама в свинцовой модели.

POPOSE: Relaxin (RLX) является преобразующим фактором роста β1 (TGF-β1) антагонистом, который, как считается, функционирует в качестве мощного коллагена, реорганизатора и основного подавляющего устройства внеклеточной матрицы. Аденовирусы (Ads) являются приемлемыми векторами для генной терапии рака. Однако неоднократное лечение Ad ограничивается краткосрочной биологической активностью в vivo. Эффективность устойчивого выражения RLX для реконструирования шрамов оценивалась с помощью инъекционной системы гели-матрицы. МАТЕРИАЛЫ И МЕТОДЫ: Шрамная ткань свиной свинины обрабатывалась с помощью рела

Совпадение в аннотации оригинала
PURPOSE: Relaxin (RLX) is a transforming growth factor-β1 (TGF-β1) antagonist that is believed to function as a potent collagen re-arranger … eased scar size, color index, and pliability. Immunohistochemistry showed decreased levels of major extracellular matrix proteins in the gel/Ad-RLX-treated group. Furthermore, treatment with gel/Ad-RLX reduced expression of tissue inhibitor of metalloproteinase-1 and alpha-smooth muscle actin and markedly increased expression of matrix metalloproteinase-1 in pig scar tissues. …

Expression and activity of matrix metallo proteinases 2 and 9 and their inhibitors in rat lungs during the perinatal period and in diaphragmatic hernia.

During lung development, the extracellular matrix undergoes dynamic remodeling. Matrix metalloproteinases (MMPs), and tissue inhibitors of matrix metalloproteinases (TIMPs), are important enzymes that participate in regulating tissue remodeling. There is an abnormal balance of the synthesis and degradation of collagen and elastin in perinatal lung associated with congenital diaphragmatic hernia (CDH). This study was designed to (1) determine the expression and gelatinolytic activity patterns of MMPs 2 and 9 and TIMPs 1 and 2 in rat lungs during the perinatal period, and (2) to test the hypothe

Spatially Resolved Proteomic Mapping in Skin Organoid for Hair Follicle Development.

Hair follicle development is a complex, highly regulated process involving interactions between epithelial and mesenchymal cells. However, the specific molecular mechanisms and important biological processes of hair follicle development remain poorly understood. How the extracellular matrix is involved in the hair follicle formation from hair germs remains to be investigated. In this study, we applied spatially resolved proteomic mapping to investigate the process of hair follicle development in skin organoids at different stages: D55, D75, D90, D140, D150, and D170, which corresponds to that

Disintegrins: integrin selective ligands which activate integrin-coupled signaling and modulate leukocyte functions.

Extracellular matrix proteins and cell adhesion receptors (integrins) play essential roles in the regulation of cell adhesion and migration. Interactions of integrins with the extracellular matrix proteins lead to phosphorylation of several intracellular proteins such as focal adhesion kinase, activating different signaling pathways responsible for the regulation of a variety of cell functions, including cytoskeleton mobilization. Once leukocytes are guided to sites of infection, inflammation, or antigen presentation, integrins can participate in the initiation, maintenance, or termination of …

Ciprofloxacin causes cytoskeletal changes and detachment of human and rat chondrocytes in vitro.

Quinolones cause damage of articular cartilage in different species by forming chelate complexes with divalent cations and inducing magnesium deficiency. Cations are important for regular function of integrins, a group of transmembrane proteins which connect extracellular matrix proteins with the intracellular cytoskeleton. We have shown that cultivation of rat chondrocytes in ciprofloxacin (CFX)-supplemented and Mg(2+)-free medium led to pronounced changes in the cytoskeleton and decreased adhesion of cells to the culture dish. In order to test whether or not these effects are species-specifi…

Collagen VI-NG2 axis in human tendon fibroblasts under conditions mimicking injury response.

In response to injury, tendon fibroblasts are activated, migrate to the wound, and contribute to tissue repair by producing and organizing t … of collagen VI to the surface of tendon fibroblasts. By interacting with NG2 proteoglycan and other extracellular matrix proteins, collagen VI regulates fibroblasts behavior and the assembly of tendon matrix, thereby playing a crucial role in tendon repair.

Inactive matrix Gla protein is elevated in patients with inflammatory bowel disease.

BACKGROUND: Matrix Gla protein (MGP) is a vitamin K dependent peptide which has an established role in suppression of vascular calcification. Recent studies have pointed to a possible link between immunomodulatory effect of MGP and inflammatory bowel disease (IBD). AIM: To compare plasma levels of dephosphorylated and uncarboxylated MGP (dp-ucMGP) between IBD patients and controls. METHODS: This cross-sectional study was conducted on 70 patients with IBD (30 patients with ulcerative colitis and 40 patients with Crohn's disease) and 60 age and gender matching healthy controls. Plasma dp-ucMGP

Extracellular matrix-targeted TNC-scFv armoring enhances CAR T cell persistence and antitumor activity in solid tumors.

Chimeric antigen receptor T cell (CAR T cell) therapy has shown limited efficacy in solid tumors, largely due to physical and immunosuppressive barriers imposed by the tumor microenvironment (TME). Tenascin-C (TNC), an extracellular matrix protein highly expressed in multiple solid malignancies, contributes to immune exclusion and T cell dysfunction. Here, we engineer an armored CAR T cell platform that locally targets the extracellular matrix by secreting a TNC-specific single-chain variable fragment (TNC-scFv) linked to conventional CAR architecture. TNC-scFv-armored CAR T cells exhibit enha

Semicircular canal morphogenesis in the zebrafish inner ear requires the function of gpr126 (lauscher), an adhesion class G protein-coupled receptor gene.

Morphogenesis of the semicircular canal ducts in the vertebrate inner ear is a dramatic example of epithelial remodelling in the embryo, and failure of normal canal development results in vestibular dysfunction. In zebrafish and Xenopus, semicircular canal ducts develop when projections of epithelium, driven by extracellular matrix production, push into the otic vesicle and fuse to form pillars. We show that in the zebrafish, extracellular matrix gene expression is high during projection outgrowth and then rapidly downregulated after fusion. Enzymatic disruption of hyaluronan in the projection

Engineering Extracellular Vesicles Secreted by Human Brain Organoids with Different Regional Identity.

Extracellular vesicles (EVs) are membrane-bound nanovesicles that show significance in intercellular communications and high therapeutic potential. In this study, a novel type of EV subpopulation, matrix-bound nanovesicles (MBVs), was identified from a decellularized extracellular matrix of brain organoids that were derived from human pluripotent stem cells to compare with supernatant EVs (SuEVs) isolated from spent media. The organoids generated 10-fold more MBVs than did SuEVs. SuEVs contained more enriched microRNA cargo than MBVs, and the microRNA relative abundance changed during organoid