bioRxiv Science⌕ Search
Home/Archive/bioRxiv

bioRxiv · 10.1101/2023.07.26.550515

Salmonella-driven Intestinal Edema in Mice is Characterized by Tensed Fibronectin Fibers

Rappold, R.·Kalogeropoulos, K.·auf dem Keller, U.·Vogel, V.·Slack, E.
View original source ↗Export metadata ↓

Abstract

Intestinal edema is a common manifestation of numerous gastrointestinal diseases and is characterized by the accumulation of fluid in the interstitial space of the intestinal wall. Technical advances in laser capture microdissection and low-biomass proteomics now allow us to specifically characterize the intestinal edema proteome. Our data identifies a high abundance of antimicrobial factors, but also highlights major contributions from the blood clotting system, extracellular matrix (ECM) and protease - protease inhibitor networks. The ECM is a complex fibrillar network of macromolecules that provides structural and mechanical support to the intestinal tissue. One abundant component of the ECM observed in the Salmonella-driven intestinal edema is the mechanosensitive glycoprotein fibronectin. Using mechanosensitive staining of fibronectin reveals a solely tensed molecular conformation of fibronectin fibers present in the edema, in contrast to other cecal tissue areas, despite the high abundance of proteases able to cleave fibronectin. Co-staining for fibrin(ogen) indicates the formation of a provisional matrix, similar to what is observed in response to skin injury. The absence of low tensional fibronectin fibers and the additional finding of a high number of protease inhibitors in the edema proteome could indicate a critical role of stretched fibronectin fibers in maintaining tissue integrity in the severely inflamed cecum. Understanding these processes may provide valuable functional diagnostic markers of intestinal disease progression. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=104 SRC="FIGDIR/small/550515v1_ufig1.gif" ALT="Figure 1"> View larger version (39K): org.highwire.dtl.DTLVardef@1318c52org.highwire.dtl.DTLVardef@1f35d21org.highwire.dtl.DTLVardef@67370borg.highwire.dtl.DTLVardef@4ec7e6_HPS_FORMAT_FIGEXP M_FIG C_FIG

Source connections

Explore related subjects

pathologyPreprint

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

Rappold, R., Kalogeropoulos, K., auf dem Keller, U., Vogel, V., Slack, E.. 2023-07-29. Salmonella-driven Intestinal Edema in Mice is Characterized by Tensed Fibronectin Fibers. https://doi.org/10.1101/2023.07.26.550515

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related preprints

bioRxiv2026

NAE1-Dependent Protein Neddylation Preserves Endothelial Identity and Vascular Integrity

Background: Endothelial dysfunction is a central driver of cardiovascular and inflammatory diseases, yet the post-translational mechanisms that preserve endothelial homeostasis remain incompletely understood. Protein neddylation, the covalent conjugation of a ubiquitin-like modifier, regulates diverse cellular processes, yet its physiological role in the vascular endothelium remains unknown. This study investigated whether protein neddylation is required to preserve endothelial identity and vascular homeostasis. Methods: We generated tamoxifen-inducible endothelial-specific Nae1 knockout mice to inhibit neddylation and combined bulk RNA sequencing, single-cell and single-nucleus transcriptomics, quantitative proteomics, biochemical analyses, and gain- and loss-of-function approaches to define the role of endothelial neddylation in vascular homeostasis and inflammatory injury. Results: Endothelial-specific Nae1 deletion caused rapid mortality associated with vascular leakage, platelet accumulation, inflammation, and multi-organ injury. Multi-omics analyses demonstrated profound loss of endothelial identity, characterized by suppression of core endothelial programs and activation of inflammatory, procoagulant, and pyroptotic pathways. Single-cell analyses revealed progressive endothelial dysfunction culminating in depletion of the endothelial population and remodeling of the vascular niche. Mechanistically, endothelial neddylation deficiency activated gasdermin D (GSDMD)- and gasdermin E (GSDME)-dependent pyroptosis, whereas dual inhibition of GSDMD and GSDME markedly attenuated inflammatory transcriptomic remodeling, vascular injury, hepatocyte death, immune cell infiltration, and platelet accumulation. Translational analyses demonstrated reduced endothelial neddylation in experimental endotoxemia and decreased expression of neddylation pathway components in human atherosclerosis and COVID-19 datasets. Conversely, restoration of endothelial neddylation partially reversed inflammatory endothelial transcriptomic reprogramming in vivo. Conclusions: NAE1-dependent protein neddylation is an essential regulator of endothelial identity and vascular integrity. Loss of endothelial neddylation promotes gasdermin-dependent pyroptosis and thrombo-inflammatory vascular injury, whereas restoration of the neddylation pathway mitigates inflammatory endothelial dysfunction. These findings identify endothelial neddylation as a fundamental mechanism maintaining vascular homeostasis and a potential therapeutic target for cardiovascular and inflammatory diseases.

pathology↗
bioRxiv2024

Natural field diagnosis and molecular confirmation of fungal and bacterial watermelon pathogens in Bangladesh: A case study from Natore and Sylhet district

The study investigated watermelon diseases in Sylhet and Natore Districts of Bangladesh, characterized by contrasting climatic conditions. Sylhet experiences lower temperatures and high rainfall, while Natore has higher temperatures and low rainfall. In these survey regions, 40 watermelon fields were selected, and 10 diseases were observed, including 4 fungal, 3 bacterial, 2 water mold, and 1 viral disease. The observed diseases were Anthracnose, Cercospora leaf spot, Fusarium wilt, Gummy stem blight, Downy mildew, Phytophthora fruit rot, Bacterial fruit blotch, Angular leaf spot, Yellow vine, and Watermelon mosaic disease. Molecular analysis was done in the Plant Pathology Lab at Sher-e-Bangla Agricultural University using the specific primers for fungal (ITS1/ITS4) and bacterial (27F/1492R) DNA regions and identified nine pathogen species, excluding the causal organism of the viral disease. The identified pathogens included Colletrotrichum orbiculare, Cercospora citrullina, Fusarium oxysporum, Stagonosporopsis cucurbitacearum, Pseudoperonospora cubensis, Phytophthora capsici, Acidovorax citrulli, Pseudomonas syringae, and Serratia marcescens. The sequencing of the identified pathogens revealed high homology (98.91-99.71%) with known sequences in the GenBank database. Phylogenetic analysis showed six clusters for fungal and water mold pathogen isolates and three for bacterial isolates where the percentages of replicate trees were 100% in all the cases. Among the identified diseases, the highest disease occurrence showed by Fusarium wilt (47.5%) following Gummy stem blight (41.5%) in the Sylhet region while Angular leaf spot (37.5%) followed Yellow vine (33%) in the Natore area. Fusarium wilt also showed high disease intensity showcasing its devastating impact on yield. The study highlights the influence of environmental conditions on disease prevalence and underscores the need for tailored management strategies. These findings provide a foundation for developing targeted disease management practices for sustainable watermelon cultivation in Bangladesh.

pathology↗
bioRxiv2024

Prevalence of GIT nematodes and associated risk factors of exotic chickens in selected farm of poultry in and around Ambo, Ethiopia

Poultry are raised worldwide in backyards and commercial systems with fewer social and religious taboos than other livestock. However, the chicken industry faces significant challenges from nematode parasites. A cross-sectional study with a random sampling technique was conducted from April to June 2019 to estimate gastrointestinal (GI) nematode parasites in chickens in selected farms in and around Ambo, Ethiopia. The fecal analysis results revealed that out of 70 samples collected, 60% were positive for gastrointestinal (GI) nematode eggs. Prevalence varied significantly by body condition, with the highest rates in chickens in poor condition (78.57%), followed by medium (54.54%) and good condition (40%). Location also played a significant role, with Ambo University Poultry Farm having the highest prevalence (83.87%), followed by Abebe Private Farm (55%) and Guder Campus Poultry Farm (26.31%). The main nematode species identified were Ascaridia galli (57.1%) and Heterakis gallinarum (2.9%). Infestation rates differed significantly by sex, age, location, and body condition, with males having higher rates of Ascaridia galli (61.53%) than females (56.14%), and Heterakis gallinarum exclusively affecting females (3.51%). Adults showed significantly higher rates of Ascaridia galli (85.71%) than young chickens (38.09%), with some infestation of Heterakis gallinarum (7.14%) observed in adults but absent in young chickens. This prevalence rate suggests limited awareness among chicken producers and insufficient control strategies in the study area. Hence, implementing targeted control strategies is advisable.

pathology↗