The extracellular matrix (ECM) is a complex meshwork of proteins forming the framework of all multicellular organisms. Protein interactions are critical to building and remodeling the ECM meshwork, while interactions between ECM proteins and their receptors are essential to initiate signal transduction. Here, we present MatriCom, a web application (https://matrinet.
View Article and Find Full Text PDFBackground: Amino acid sequence characterization is a fundamental part of virtually any protein analysis, and creating concise and clear protein topology schemes is of high importance in proteomics studies. Although numerous databases and prediction servers exist, it is challenging to incorporate data from various, and sometimes contending, resources into a publication-ready scheme.
Results: Here, we present the Protein Topology Deviser R package (ProToDeviseR) for the automatic generation of protein topology schemes from database accession numbers, raw results from multiple prediction servers, or a manually prepared table of features.
Male infertility is a multifactorial condition for which the underlying causes frequently remain undefined. Genetic factors have long been associated with male fertility. However, many of them are poorly or not at all characterized and their biological functions are unknown.
View Article and Find Full Text PDFThe ECM is a complex and dynamic meshwork of proteins that forms the framework of all multicellular organisms. Protein interactions within the ECM are critical to building and remodeling the ECM meshwork, while interactions between ECM proteins and cell surface receptors are essential for the initiation of signal transduction and the orchestration of cellular behaviors. Here, we report the development of MatriCom, a web application (https://matrinet.
View Article and Find Full Text PDFEffective interplay between the uterus and the embryo is essential for pregnancy establishment; however, convenient methods to screen embryo implantation success and maternal uterine response in experimental mouse models are currently lacking. Here, we report 3DMOUSEneST, a groundbreaking method for analyzing mouse implantation sites based on label-free higher harmonic generation microscopy, providing unprecedented insights into the embryo-uterine dynamics during early pregnancy. The 3DMOUSEneST method incorporates second-harmonic generation microscopy to image the three-dimensional structure formed by decidual fibrillar collagen, named 'decidual nest', and third-harmonic generation microscopy to evaluate early conceptus (defined as the embryo and extra-embryonic tissues) growth.
View Article and Find Full Text PDFJ Cardiovasc Transl Res
December 2024
Myocardial fibrosis is a common finding in victims of sudden cardiac death (SCD). Whole exome sequencing was performed in 127 victims of SCD with primary myocardial fibrosis as the only pathological finding. These cases are derived from the Fingesture study which has collected data from autopsy-verified SCD victims in Northern Finland.
View Article and Find Full Text PDFRenal development is a complex process in which two major processes, tubular branching and nephron development, regulate each other reciprocally. Our previous findings have indicated that collagen XVIII (ColXVIII), an extracellular matrix protein, affects the renal branching morphogenesis. We investigate here the role of ColXVIII in nephron formation and the behavior of nephron progenitor cells (NPCs) using isoform-specific ColXVIII knockout mice.
View Article and Find Full Text PDFCollagen biosynthesis requires several co- and post-translational modifications of lysine and proline residues to form structurally and functionally competent collagen molecules. Formation of 4-hydroxyproline (4Hyp) in Y-position prolines of the repetitive -X-Y-Gly- sequences provides thermal stability for the triple-helical collagen molecules. 4Hyp formation is catalyzed by a collagen prolyl 4-hydroxylase (C-P4H) family consisting of three isoenzymes.
View Article and Find Full Text PDFThe extracellular matrix (ECM) is a complex meshwork of proteins that forms the scaffold of all tissues in multicellular organisms. It plays crucial roles in all aspects of life - from orchestrating cell migration during development, to supporting tissue repair. It also plays critical roles in the etiology or progression of diseases.
View Article and Find Full Text PDFThe desmoplastic reaction observed in many cancers is a hallmark of disease progression and prognosis, particularly in breast and pancreatic cancer. Stromal-derived extracellular matrix (ECM) is significantly altered in desmoplasia, and as such plays a critical role in driving cancer progression. Using fibroblast-derived matrices (FDMs), we show that cancer cells have increased growth on cancer associated FDMs, when compared to FDMs derived from non-malignant tissue (normal) fibroblasts.
View Article and Find Full Text PDFJ Clin Invest
September 2023
The tumor extracellular matrix (ECM) critically regulates cancer progression and treatment response. Expression of the basement membrane component collagen XVIII (ColXVIII) is induced in solid tumors, but its involvement in tumorigenesis has remained elusive. We show here that ColXVIII was markedly upregulated in human breast cancer (BC) and was closely associated with a poor prognosis in high-grade BCs.
View Article and Find Full Text PDFUnlabelled: The extracellular matrix (ECM) is a complex meshwork of proteins that forms the scaffold of all tissues in multicellular organisms. It plays critical roles in all aspects of life: from orchestrating cell migration during development, to supporting tissue repair. It also plays critical roles in the etiology or progression of diseases.
View Article and Find Full Text PDFInvest Ophthalmol Vis Sci
October 2022
Purpose: Defects in the iridocorneal angle tissues, including the trabecular meshwork (TM) and Schlemm's canal (SC), impair aqueous humor flow and increase the intraocular pressure (IOP), eventually resulting in glaucoma. Activation of endothelial tyrosine kinase receptor Tie2 by angiopoietin-1 (Angpt1) has been demonstrated to be essential for SC formation, but roles of the other two Tie2 ligands, Angpt2 and Angpt4, have been controversial or not yet characterized, respectively.
Methods: Angpt4 expression was investigated using genetic cell fate mapping and reporter mice.
J Cell Sci
September 2022
The roles of the extracellular matrix molecule tenascin-C (TNC) in health and disease have been extensively reviewed since its discovery over 40 years ago. Here, we will describe recent insights into the roles of TNC in tumorigenesis, angiogenesis, immunity and metastasis. In addition to high levels of expression in tumors, and during chronic inflammation, and bacterial and viral infection, TNC is also expressed in lymphoid organs.
View Article and Find Full Text PDFIntegrin α11β1 is a collagen-binding integrin that is needed to induce and maintain the myofibroblast phenotype in fibrotic tissues and during wound healing. The expression of the α11 is upregulated in cancer-associated fibroblasts (CAFs) in various human neoplasms. We investigated α11 expression in human cutaneous squamous cell carcinoma (cSCC) and in benign and premalignant human skin lesions and monitored its effects on cSCC development by subjecting α11-knockout ( ) mice to the DMBA/TPA skin carcinogenesis protocol.
View Article and Find Full Text PDFProper deposition of the extracellular matrix and its major components, the collagens, is essential for endochondral ossification and bone mass accrual. Collagen prolyl 4-hydroxylases (C-P4Hs) hydroxylate proline residues in the -X-Pro-Gly- repeats of all known collagen types. Their product, 4-hydroxyproline, is essential for correct folding and thermal stability of the triple-helical collagen molecules in physiological body temperatures.
View Article and Find Full Text PDFThe extracellular matrix (ECM) is a three-dimensional network of proteins of diverse nature, whose interactions are essential to provide tissues with the correct mechanical and biochemical cues they need for proper development and homeostasis. Changes in the quantity of extracellular matrix (ECM) components and their balance within the tumor microenvironment (TME) accompany and fuel all steps of tumor development, growth and metastasis, and a deeper and more systematic understanding of these processes is fundamental for the development of future therapeutic approaches. The wealth of "big data" from numerous sources has enabled gigantic steps forward in the comprehension of the oncogenic process, also impacting on our understanding of ECM changes in the TME.
View Article and Find Full Text PDFThe extracellular matrix (ECM) is a fundamental component of the tissue of multicellular organisms that is comprised of an intricate network of multidomain proteins and associated factors, collectively known as the matrisome. The ECM creates a biophysical environment that regulates essential cellular processes such as adhesion, proliferation and migration and impacts cell fate decisions. The composition of the ECM varies across organs, developmental stages and diseases.
View Article and Find Full Text PDFNeurocase
February 2022
. gene mutations have been associated with Knobloch syndrome, which is characterized by ocular and brain abnormalities. Here we report a 4.
View Article and Find Full Text PDFBackground: The reported prevalence of Alport syndrome varies from one in 5000 to one in 53,000 individuals. This study estimated the frequencies of predicted pathogenic variants in sequencing databases of populations without known kidney disease.
Methods: Predicted pathogenic variants were identified using filtering steps based on the ACMG/AMP criteria, which considered collagen IV 3-5 position 1 Gly to be critical domains.
Arterioscler Thromb Vasc Biol
July 2021
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View Article and Find Full Text PDFOsteoarthritis (OA) is the most prevalent chronic joint disease that affects a large proportion of the elderly population. Chondrogenic progenitor cells (CPCs) reside in late-stage OA cartilage tissue, producing a fibrocartilaginous extracellular matrix; these cells can be manipulated to deposit proteins of healthy articular cartilage. CPCs are under the control of SOX9 and RUNX2.
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