Endothelial eNOS deficiency causes podocyte injury through NFAT2 and heparanase in diabetic mice.

The pivotal role of endothelial nitric oxide synthase (eNOS) in diabetic nephropathy (DN) has been demonstrated using global eNOS knockout (eNOSGKO) mice. However, the precise role of endothelially expressed eNOS and how its deficiency advances DN are still unclear. Here, we targeted endothelial eNOS expression (E-eNOSKO) after the onset of diabetes using the floxed eNOS and endSCL-CreER alleles.

Specific 3-O-sulfated heparan sulfate domains regulate salivary gland basement membrane metabolism and epithelial differentiation.

Heparan sulfate (HS) regulation of FGFR function, which is essential for salivary gland (SG) development, is determined by the immense structural diversity of sulfated HS domains. 3-O-sulfotransferases generate highly 3-O-sulfated HS domains (3-O-HS), and Hs3st3a1 and Hs3st3b1 are enriched in myoepithelial cells (MECs) that produce basement membrane (BM) and are a growth factor signaling hub. Hs3st3a1;Hs3st3b1 double-knockout (DKO) mice generated to investigate 3-O-HS regulation of MEC function and growth factor signaling show loss of specific highly 3-O-HS and increased FGF/FGFR complex binding to HS.

Collagen-Heparin-FGF2-VEGF Scaffolds Induce a Regenerative Gene Expression Profile in a Fetal Sheep Wound Model.

Background: The developmental abnormality spina bifida is hallmarked by missing tissues (e.g. skin) and exposure of the spinal cord to the amniotic fluid, which can negatively impact neurological development.

Epigenetic Targeting of Heparan Sulfate 3-- and 6--Sulfation in Breast Cancer Cells: Prospects for Attenuating Prothrombotic Tumor Cell Activities.

The deregulation of cell surface heparan sulfate proteoglycans (HSPGs) is a main issue of cancer cells for increasing their malignancy. In these terms, the sulfation pattern of HS, created by an orchestrated activity of enzymes balancing a site-specific sulfation, is of key importance. These enzymes are often deregulated by epigenetic processes in cancer, e.

Elastogenesis in Focus: Navigating Elastic Fibers Synthesis for Advanced Dermal Biomaterial Formulation.

Elastin, a fibrous extracellular matrix (ECM) protein, is the main component of elastic fibers that are involved in tissues' elasticity and resilience, enabling them to undergo reversible extensibility and to endure repetitive mechanical stress. After wounding, it is challenging to regenerate elastic fibers and biomaterials developed thus far have struggled to induce its biosynthesis. This review provides a comprehensive summary of elastic fibers synthesis at the cellular level and its implications for biomaterial formulation, with a particular focus on dermal substitutes.

Identification of heparin-binding amino acid residues in antibody HS4C3 with the potential to design antibodies against heparan sulfate domains.

Heparan sulfate (HS) is a linear polysaccharide with high structural and functional diversity. Detection and localization of HS in tissues can be performed using single chain variable fragment (scFv) antibodies. Although several anti-HS antibodies recognizing different sulfation motifs have been identified, little is known about their interaction with HS.

Matrisomal components involved in regenerative wound healing in axolotl and : implications for biomaterial development.

Achieving regeneration in humans has been a long-standing goal of many researchers. Whereas amphibians like the axolotl () are capable of regenerating whole organs and even limbs, most mammals heal their wounds fibrotic scarring. Recently, the African spiny mouse ( sp.

Heparin-resistance in AL amyloidosis: a case report.

Background: Non-AT-III mediated heparin-resistance during CPB occurs by complex-forming with heparin-binding proteins. Currently, there are no specific recommendations for non-AT-III mediated heparin-resistance.

Case Presentation: We present a fatal case of a 70-yr-old male-patient undergoing cardiac-surgery in which refractory heparin-resistance was observed.

Peroxisome proliferator-activated receptor ɣ agonist mediated inhibition of heparanase expression reduces proteinuria.

Background: Proteinuria is associated with many glomerular diseases and a risk factor for the progression to renal failure. We previously showed that heparanase (HPSE) is essential for the development of proteinuria, whereas peroxisome proliferator-activated receptor ɣ (PPARɣ) agonists can ameliorate proteinuria. Since a recent study showed that PPARɣ regulates HPSE expression in liver cancer cells, we hypothesized that PPARɣ agonists exert their reno-protective effect by inhibiting glomerular HPSE expression.

Gene expression profiles in mesenchymal stromal cells from bone marrow, adipose tissue and lung tissue of COPD patients and controls.

Background: Chronic obstructive pulmonary disease (COPD) is characterized by irreversible lung tissue damage. Novel regenerative strategies are urgently awaited. Cultured mesenchymal stem/stromal cells (MSCs) have shown promising results in experimental models of COPD, but differences between sources may impact on their potential use in therapeutic strategies in patients.

Initial Steps towards Spatiotemporal Signaling through Biomaterials Using Click-to-Release Chemistry.

The process of wound healing is a tightly controlled cascade of events, where severe skin wounds are resolved via scar tissue. This fibrotic response may be diminished by applying anti-fibrotic factors to the wound, thereby stimulating regeneration over scarring. The development of tunable biomaterials that enable spatiotemporal control over the release of anti-fibrotics would greatly benefit wound healing.

A collagen plug with shape memory to seal iatrogenic fetal membrane defects after fetoscopic surgery.

Iatrogenic preterm premature rupture of fetal membranes (iPPROM) after fetal surgery remains a strong trigger for premature birth. As fetal membrane defects do not heal spontaneously and amniotic fluid leakage and chorioamniotic membrane separation may occur, we developed a biocompatible, fetoscopically-applicable collagen plug with shape memory to prevent leakage. This plug expands directly upon employment and seals fetal membranes, hence preventing amniotic fluid leakage and potentially iPPROM.

CGRP inhibits human Langerhans cells infection with HSV by differentially modulating specific HSV-1 and HSV-2 entry mechanisms.

Herpes simplex virus (HSV) is widespread globally, with both HSV-1 and HSV-2 responsible for genital herpes. During sexual transmission, HSV targets epithelial cells, sensory peripheral pain neurons secreting the mucosal neuropeptide calcitonin gene-related peptide (CGRP), and mucosal immune cells including Langerhans cells (LCs). We previously described a neuro-immune crosstalk, whereby CGRP inhibits LCs-mediated human immunodeficiency virus type 1 (HIV-1) transmission.

Blocking of inflammatory heparan sulfate domains by specific antibodies is not protective in experimental glomerulonephritis.

Glomerulonephritis is an acquired serious glomerular disease, which involves the interplay of many factors such as cytokines, chemokines, inflammatory cells, and heparan sulfate (HS). We previously showed that blocking of inflammatory heparan sulfate domains on cultured glomerular endothelium by specific anti-HS single chain antibodies reduced polymorphonuclear cell (PMN) adhesion and chemokine binding. We hypothesized that injection of anti-HS antibodies in PMN-driven experimental glomerulonephritis should reduce glomerular influx of PMNs and thereby lead to a better renal outcome.

4-Deoxy-4-fluoro-GalNAz (4FGalNAz) Is a Metabolic Chemical Reporter of O-GlcNAc Modifications, Highlighting the Notable Substrate Flexibility of O-GlcNAc Transferase.

Bio-orthogonal chemistries have revolutionized many fields. For example, metabolic chemical reporters (MCRs) of glycosylation are analogues of monosaccharides that contain a bio-orthogonal functionality, such as azides or alkynes. MCRs are metabolically incorporated into glycoproteins by living systems, and bio-orthogonal reactions can be subsequently employed to install visualization and enrichment tags.

Parietal epithelial cells maintain the epithelial cell continuum forming Bowman's space in focal segmental glomerulosclerosis.

In the glomerulus, Bowman's space is formed by a continuum of glomerular epithelial cells. In focal segmental glomerulosclerosis (FSGS), glomeruli show segmental scarring, a result of activated parietal epithelial cells (PECs) invading the glomerular tuft. The segmental scars interrupt the epithelial continuum.

Loss of Hs3st3a1 or Hs3st3b1 enzymes alters heparan sulfate to reduce epithelial morphogenesis and adult salivary gland function.

Heparan sulfate 3-O-sulfotransferases generate highly sulfated but rare 3-O-sulfated heparan sulfate (HS) epitopes on cell surfaces and in the extracellular matrix. Previous ex vivo experiments suggested functional redundancy exists among the family of seven enzymes but that Hs3st3a1 and Hs3st3b1 sulfated HS increases epithelial FGFR signaling and morphogenesis. Single-cell RNAseq analysis of control SMGs identifies increased expression of Hs3st3a1 and Hs3st3b1 in endbud and myoepithelial cells, both of which are progenitor cells during development and regeneration.

Selective Binding of Heparin/Heparan Sulfate Oligosaccharides to Factor H and Factor H-Related Proteins: Therapeutic Potential for C3 Glomerulopathies.

Complement dysregulation is characteristic of the renal diseases atypical hemolytic uremic syndrome (aHUS) and complement component 3 glomerulopathy (C3G). Complement regulatory protein Factor H (FH) inhibits complement activity, whereas FH-related proteins (FHRs) lack a complement regulatory domain. FH and FHRs compete for binding to host cell glycans, in particular heparan sulfates (HS).

Polarized Secretion of APRIL by the Tonsil Epithelium Upon Toll-Like Receptor Stimulation.

In mucosa such as tonsil, antibody-producing plasmocytes (PCs) lie in sub-epithelium space, which is thought to provide a suitable environment for their survival. A proliferation inducing ligand (APRIL) is one key survival factor for PCs present in this area. According to staining, apical epithelial cells produced APRIL, and the secreted product had to migrate all through the stratified surface epithelium to reach basal cells.

The role of MMP-14 in ovarian cancer: a systematic review.

Aim: In order to evaluate the role of MMP-14 in ovarian cancer, a systematic review was conducted.

Methods: In March 2020, a search in Pubmed was performed with MMP-14 and ovarian cancer as search terms. After exclusion of the references not on MMP-14 or ovarian cancer or not in English, the studies found were classified into two categories: basic research and clinicopathological research.

Regulation of fractone heparan sulfate composition in young and aged subventricular zone neurogenic niches.

Fractones, specialized extracellular matrix structures found in the subventricular zone (SVZ) neurogenic niche, can capture growth factors, such as basic fibroblast growth factor, from the extracellular milieu through a heparin-binding mechanism for neural stem cell (NSC) presentation, which promotes neurogenesis. During aging, a decline in neurogenesis correlates with a change in the composition of heparan sulfate (HS) within fractones. In this study, we used antibodies that recognize specific short oligosaccharides with varying sulfation to evaluate the HS composition in fractones in young and aged brains.

Low-GDP, pH-neutral solutions preserve peritoneal endothelial glycocalyx during long-term peritoneal dialysis.

Background: During peritoneal dialysis (PD), solute transport and ultrafiltration are mainly achieved by the peritoneal blood vasculature. Glycocalyx lies on the surface of endothelial cells and plays a role in vascular permeability. Low-glucose degradation product (GDP), pH-neutral PD solutions reportedly offer higher biocompatibility and lead to less peritoneal injury.

Growth factor mimetics for skin regeneration: In vitro profiling of primary human fibroblasts and keratinocytes.

Small molecules have gained considerable interest in regenerative medicine, as they can effectively modulate cell fates in a spatiotemporal controllable fashion. A continuous challenge in the field represents genuine mimicry or activation of growth factor signaling with small molecules. Here, we selected and profiled three compounds for their capacity to directly or indirectly activate endogenous FGF-2, VEGF, or SHH signaling events in the context of skin regeneration.

Evaluation and Refinement of Sample Preparation Methods for Extracellular Matrix Proteome Coverage.

The extracellular matrix is a key component of tissues, yet it is underrepresented in proteomic datasets. Identification and evaluation of proteins in the extracellular matrix (ECM) has proved challenging due to the insolubility of many ECM proteins in traditional protein extraction buffers. Here we separate the decellularization and ECM extraction steps of several prominent methods for evaluation under real-world conditions.