Alterations In Tissue Structure Research Articles

Ultrasound Viscoelastography by Acoustic Radiation Force: A State-of-the-Art Review.

Ultrasound elastography (USE) is a promising tool for tissue characterization as several diseases result in alterations of tissue structure and composition, which manifest as changes in tissue mechanical properties. By imaging the tissue response to an applied mechanical excitation, USE mimics the manual palpation performed by clinicians to sense the tissue elasticity for diagnostic purposes. Next to elasticity, viscosity has recently been investigated as an additional, relevant, diagnostic biomarker. Moreover, since biological tissues are inherently viscoelastic, accounting for viscosity in the tissue characterization process enhances the accuracy of the elasticity estimation. Recently, methods exploiting different acquisition and processing techniques have been proposed to perform ultrasound viscoelastography. After introducing the physics describing viscoelasticity, a comprehensive overview of the currently available USE acquisition techniques is provided, followed by a structured review of the existing viscoelasticity estimators classified according to the employed processing technique. These estimators are further reviewed from a clinical usage perspective, and current outstanding challenges are discussed.

Expression of Concern: Refat et al. Antioxidant, Antigenotoxic, and Hepatic Ameliorative Effects of Quercetin/Zinc Complex on Cadmium-Induced Hepatotoxicity and Alterations in Hepatic Tissue Structure. Coatings 2021, 11, 501

With this notice, the Editorial Office of Coatings states its awareness of the concerns relating to both the authorship and research integrity of the published paper “Antioxidant, Antigenotoxic, and Hepatic Ameliorative Effects of Quercetin/Zinc Complex on Cadmium-Induced Hepatotoxicity and Alterations in Hepatic Tissue Structure” [...]

High resolution fluorescence imaging of the alveolar scaffold as a novel tool to assess lung injury

Acute lung injury (ALI) represents an aetiologically diverse form of pulmonary damage. Part of the assessment and diagnosis of ALI depends on skilled observer-based scoring of brightfield microscopy tissue sections. Although this readout is sufficient to determine gross alterations in tissue structure, its categorical scores lack the sensitivity to describe more subtle changes in lung morphology. To generate a more sensitive readout of alveolar perturbation we carried out high resolution immunofluorescence imaging on 200 μm lung vibratome sections from baseline and acutely injured porcine lung tissue, stained with a tomato lectin, Lycopersicon Esculentum Dylight-488. With the ability to resolve individual alveoli along with their inner and outer wall we generated continuous readouts of alveolar wall thickness and circularity. From 212 alveoli traced from 10 baseline lung samples we established normal distributions for alveolar wall thickness (27.37; 95% CI [26.48:28.26]) and circularity (0.8609; 95% CI [0.8482:0.8667]) in healthy tissue. Compared to acutely injured lung tissue baseline tissue exhibited a significantly lower wall thickness (26.86 ± 0.4998 vs 50.55 ± 4.468; p = 0.0003) and higher degree of circularityϕ≤ (0.8783 ± 0.01965 vs 0.4133 ± 0.04366; p < 0.0001). These two components were subsequently combined into a single more sensitive variable, termed the morphological quotient (MQ), which exhibited a significant negative correlation (R2 = 0.9919, p < 0.0001) with the gold standard of observer-based scoring. Through the utilisation of advanced light imaging we show it is possible to generate sensitive continuous datasets describing fundamental morphological changes that arise in acute lung injury. These data represent valuable new analytical tools that can be used to precisely benchmark changes in alveolar morphology both in disease/injury as well as in response to treatment/therapy.

Epidemiological Survey on Post Mortem Coccidiosis in Broiler Chicken in Bejaia Province, Northern Algeria.

The epidemiological survey was carried out to determine the prevalence of eimeriosis in broiler chickens slaughtered depending the season, to determine the different Eimeria species causing the coccidiosis in poultry farms; and to assess the impact of Eimeria parasite on histomorphological structure and oxidative stress parameters of the intestine. The study was conducted from December 2018 to December 2019 in the province of Bejaia, Algeria. The intestines chickens (n = 366) were obtained immediately after slaughter, each cut into different segments (duodenum, jejunum, ileum, and caecum). Microscopic and parasitological examinations were performed according to standard procedures. Histomorphometric measurements of intestine were obtained using Image J software. Oxidative stress parameters were carried out from intestine tissue. Eimeria spp. were detected in 73.77% (95% CI 71.20-76.34) of broiler gut samples. The prevalence varied significantly according to the season, with the lowest rates in winter (42.81%, 95% CI 40.35-45.27) and the highest in autumn (97.92%, 95% CI 97.6-99.4). All seven Eimeria species were identified, most commonly E. necatrix (27.70%), E. brunetti (26.47%), and E. tenella (20.96%). The mean lesion score ranged from 1.51 ± 0.05 to 1.79 ± 0.04. Significant differences in VH/CD ratio of intestinal epithelium (P < 0.001) were observed in different intestinal portions of infested broiler chickens compared to non-infested. The mean MDA concentration of intestinal segments was significantly higher in Eimeria species infested broilers compared to non-infested (P < 0.05). The results show at least one difference in CAT, SOD, and ABTS-+ concentrations (P < 0.05) in both chicken's groups. Our results revealed that coccidiosis is extremely prevalent in slaughtered broilers, with an abundance of pathogenic Eimeria species. Also, it was concluded that infestation induces tissue structure alterations which coincides with the oxidative damage.

Histopathology and Phylogeny of the Dinoflagellate Hematodinium perezi and the Epibiotic Peritrich Ciliate Epistylis sp. Infecting the Blue Crab Callinectes sapidus in the Eastern Mediterranean.

Bioinvasions constitute both a direct and an indirect threat to ecosystems. Direct threats include pressures on local trophic chains, while indirect threats might take the form of an invasion of a microorganism alongside its host. The marine dinoflagellate Hematodinium perezi, parasitizing blue crabs (Callinectes sapidus), has a worldwide distribution alongside its host. In Greece, fluctuations in the blue crab population are attributed to overexploitation and the effects of climate change. The hypothesis of the present study was that blue crab population reductions cannot only be due to these factors, and that particular pathogens may also be responsible for the fluctuations. To investigate this hypothesis, both lethargic and healthy blue crab specimens were collected from three different fishing sites in order to assess the health status of this important species. Together with the lethargic responses, the hemolymph of the infested crabs presented a milky hue, indicating the first signs of parasitic infestation with H. perezi. The histopathological results and molecular identification demonstrated the effect of the presence of H. perezi in the internal organs and their important role in the mortality of blue crabs. Specifically, H. perezi, in three different tissues examined (heart, gills, hepatopancreas), affected the hemocytes of the species, resulting in alterations in tissue structure. Apart from this dinoflagellate parasite, the epibiotic peritrich ciliate Epistylis sp. was also identified, infecting the gills. This study represents the first detection of H. perezi in the eastern Mediterranean, demonstrating that this is the main causative agent of blue crab mortality on Greek coastlines.

IGFBP5 is released by senescent cells and is internalized by healthy cells, promoting their senescence through interaction with retinoic receptors

Cells that are exposed to harmful genetic damage, either from internal or external sources, may undergo senescence if they are unable to repair their DNA. Senescence, characterized by a state of irreversible growth arrest, can spread to neighboring cells through a process known as the senescence-associated secretory phenotype (SASP). This phenomenon contributes to both aging and the development of cancer. The SASP comprises a variety of factors that regulate numerous functions, including the induction of secondary senescence, modulation of immune system activity, remodeling of the extracellular matrix, alteration of tissue structure, and promotion of cancer progression. Identifying key factors within the SASP is crucial for understanding the underlying mechanisms of senescence and developing effective strategies to counteract cellular senescence. Our research has specifically focused on investigating the role of IGFBP5, a component of the SASP observed in various experimental models and conditions.Through our studies, we have demonstrated that IGFBP5 actively contributes to promoting senescence and can induce senescence in neighboring cells. We have gained valuable insights into the mechanisms through which IGFBP5 exerts its pro-senescence effects. These mechanisms include its release following genotoxic stress, involvement in signaling pathways mediated by reactive oxygen species and prostaglandins, internalization via specialized structures called caveolae, and interaction with a specific protein known as RARα. By uncovering these mechanisms, we have advanced our understanding of the intricate role of IGFBP5 in the senescence process. The significance of IGFBP5 as a pro-aging factor stems from an in vivo study we conducted on patients undergoing Computer Tomography analysis. In these patients, we observed an elevation in circulating IGFBP5 levels in response to radiation-induced organismal stress.Globally, our findings highlight the potential of IGFBP5 as a promising therapeutic target for age-related diseases and cancer.

Effect of indoxyl sulfate on the morphology and function of the thyroid gland - ex vivo studies in rabbits.

Indoxyl sulfates are uremic indolic toxins known to participate in the pathogenesis of cardiovascular diseases during chronic kidney disease in humans and some animal species. However, nothing is known about the indoxyl sulfate effect on the thyroid gland which is especially responsible for the general organism metabolism. This study determines the morpho-functional status of the thyroid gland after exposure to indoxyl sulfate (10, 25, and 50 mM) with the use of an ex vivo system and rabbit (n=10) as an experimental model thyroid gland histology, immunoexpression of thyrotropin receptor (TSHR), and concentrations of thyroxine (T4) and triiodothyronine (T3) were evaluated. Statistical analyses were performed using one-way analysis of the variance (ANOVA) followed by Tukey's post hoc comparison test. Minor alterations in thyroid tissue structure e.g. very rare exfoliated epithelial cells, condensed colloid fluid, or slight loosening of the epithelium were found. In addition, modulated dose dependent-expression of TSHR (p<0.01, p<0.001) together with a decreased level of T4 and T3 (p<0.001, p<0.01) exception of an increased level of T4 after the middle dose of indoxyl sulfate were revealed. We report here, for the first time, that indoxyl sulfate affects the thyroid gland mainly at the molecular level. The rabbit thyroid gland ex vivo system seems to be suitable for further studies on the thyroid gland in health and disease. However, the effect of TSH-TSHR signaling at ultrastructural, and epigenetic levels needs supplementary appraisal.

Enrofloxacin hydrochloride toxicological effects on crucian carp reflected by serological changes and neurotoxicity

Due to its water solubility and wide applicability, enrofloxacin hydrochloride (EH) may enter aquatic ecosystems and cause negative effects on aquatic organisms. This study aimed to explore toxicological effects via serological changes and neurotoxicity, which were induced by EH exposure in crucian carp (Carassius auratus var. Pengze). The drug residues in brain tissue and protein content in serum were determined to analyze serological changes. Alterations in brain tissue structure and function, cerebral microvessels permeability, and the expressions of gene and protein regarding blood-brain barrier (BBB) were studied to reflect the neurotoxicity. Employing a validated high-performance liquid chromatography (HPLC) method, EH residues could be detected at various time-points throughout the experiment. Enzyme-linked immunosorbent assay (ELISA) showed that EH increased the levels of S100B, NSE and GFAP proteins in serum. Additionally, there was a significant positive correlation between serum S100B, NSE protein contents and EH residues (P < 0.05). Hematoxylin and eosin (H&E) staining revealed brain damage from EH exposure by the formation of vacuoles in brain glial cells, pyknosis of the nucleus, and a decrease in cell population density. Transmission electron microscope (TEM) revealed morphological changes in microvessels and condensation of astrocyte nucleus. Evans blue (EB) permeability test visualized an obvious increase in cerebral microvessels leakage. The real-time quantitative PCR (qPCR) results indicated that EH up-regulated the mRNA expression levels of S100B, NSE and GFAP, down-regulated the mRNA expression levels of P-gp, ZO-1, Occludin and Claudin-5. The Western blot (WB) results demonstrated increased NSE and GFAP protein expressions, decreased P-gp and Occludin protein expressions following EH exposure in brain, in consistent with the gene expressions, respectively. In conclusion, these findings indicated that EH brought about marked rise in serum biomarker levels and disrupted the central nervous system (CNS) of crucian carp. These data would help elucidate the mechanism underlying EH-induced neurotoxicological effects.

Effects of vitamin C on transport of Penaeus monodon

The experiment simulated the logistical transportation of Penaeus monodon. It set four distinct gradient Vitamin C (Vc) addition levels, including 0mg/L, 111mg/L, 222mg/L, and 333mg/L, to investigate the impact of Vc on the anti-stress ability of P. monodon during transportation. And the survival rate following transportation and a 15-day interim rearing period were recorded. Moreover, the alterations in tissue structure and activity of the enzymes alkaline phosphatase (ACP), alkaline phosphatase (AKP), total superoxide dismutase (T-SOD), and total superoxide dismutase (T-AOC) were checked. The results showed that with the increase of Vc supplemental level, the survival rate of P. monodon after transportation and after 15 days of temporary rearing increased to varying degrees. ACP and AKP in the hepatopancreas increased first and then decreased. T-SOD activity in the 0mg/L group was the lowest and then decreased gradually. The activity of total antioxidant capacity (T-AOC) in the 0mg/L group was the lowest and then stabilized. The branchial tissue structure also changed. The branchial tissue blood cell disorder decreased, the diaphragm gradually narrowed, the cornered cortex gradually recovered, and the swelling decreased. In conclusion, Vc positively affects the survival rate of P. monodon after transportation and temporary cultivation and alleviates the stress of P. monodon. The amount of Vc added at about 333mg/Lin, the transportation of P. monodon could play a positive role. The experimental results provide primary data for the transportation of P. monodon.

Histological tissue structure alterations resulting from Staphylococcus aureus intramammary infection in heifer mammary glands hormonally induced to rapidly grow and develop

Intramammary infections (IMI) are common in nonlactating dairy cattle and are expected to impair mammary growth and development and reduce future milk production. The objective of this study was to histologically evaluate how IMI alter tissue structure in growing and developing heifer mammary glands. A total of 18 nonpregnant, nonlactating heifers between 11 and 14 mo of age were used in the present study. Heifers received daily supraphysiological injections of estradiol and progesterone for 14 d to stimulate rapid mammary growth and development. One-quarter of each heifer was subsequently infused with Staphylococcus aureus (CHALL) while a second quarter served as an uninfected control (UNINF). Heifers were randomly selected and euthanized either the last day of hormonal injections to observe IMI effects on mammary gland growth (GRO), or 13 d post-injections, to observe IMI effects on mammary development (DEV). Mammary tissues were collected from the center and edge parenchymal regions of each mammary gland for morphometric tissue area evaluation. For GRO tissues, CHALL quarters had less epithelial tissue area and marginally more intralobular stroma tissue area than UNINF quarters. Tissue areas occupied by luminal space, extralobular stroma, adipose, and lobular tissue were similar. For DEV tissues, area occupied by epithelium, luminal space, intralobular stroma, and extralobular stroma did not differ between quarter treatments, but UNINF quarters had more adipose tissue area and marginally less lobular area than CHALL quarters. Results indicate that IMI in growing and developing mammary glands reduces mammary epithelial growth and alters mammary gland development by impairing epithelial branching into the mammary fat pad. Taken together, these tissue changes before calving may have adverse effects on milk production. Therefore, an important focus should be placed on improving udder health in replacement heifers through management strategies that mitigate the deleterious effects of IMI and promote the positive development of the mammary gland.

Transcriptome analysis of pika heart tissue reveals mechanisms underlying the adaptation of a keystone species on the roof of the world.

High-altitude environments impose intense stresses on living organisms and drive striking phenotypic and genetic adaptations, such as hypoxia resistance, cold tolerance, and increases in metabolic capacity and body mass. As one of the most successful and dominant mammals on the Qinghai-Tibetan Plateau (QHTP), the plateau pika (Ochotona curzoniae) has adapted to the extreme environments of the highest altitudes of this region and exhibits tolerance to cold and hypoxia, in contrast to closely related species that inhabit the peripheral alpine bush or forests. To explore the potential genetic mechanisms underlying the adaptation of O. curzoniae to a high-altitude environment, we sequenced the heart tissue transcriptomes of adult plateau pikas (comparing specimens from sites at two different altitudes) and Gansu pikas (O. cansus). Differential expression analysis and weighted gene co-expression network analysis (WGCNA) were used to identify differentially expressed genes (DEGs) and their primary functions. Key genes and pathways related to high-altitude adaptation were identified. In addition to the biological processes of signal transduction, energy metabolism and material transport, the identified plateau pika genes were mainly enriched in biological pathways such as the negative regulation of smooth muscle cell proliferation, the apoptosis signalling pathway, the cellular response to DNA damage stimulus, and ossification involved in bone maturation and heart development. Our results showed that the plateau pika has adapted to the extreme environments of the QHTP via protection against cardiomyopathy, tissue structure alterations and improvements in the blood circulation system and energy metabolism. These adaptations shed light on how pikas thrive on the roof of the world.

Resolution to Expression of Concern: “Refat et al. Antioxidant, Antigenotoxic, and Hepatic Ameliorative Effects of Quercetin/Zinc Complex on Cadmium-Induced Hepatotoxicity and Alterations in Hepatic Tissue Structure. Coatings 2021, 11, 501”

The journal’s editorial office and journal editors are jointly issuing a resolution to the Expression of Concern [...]

Implication of P2Y12 receptor in uc.48+-mediated abnormal sympathoexcitatory reflex via superior cervical ganglia in myocardial ischemic rats

Purinergic 2Y12 (P2Y12) receptor antagonists are used as platelet aggregation inhibitors. Long non-coding RNAs (lncRNAs) play an important role in neuropathological events. Satellite glial cells (SGCs) in the superior cervical ganglia (SCGs) encircle the somata of neurons. This study explored if the upregulated P2Y12 receptor in SCGs was relevant to lncRNA uc.48+ during myocardial ischemia (MI). The results showed that upregulation of P2Y12 receptor was accompanied by increased expression of uc.48+ in the SCGs of MI rats which displayed abnormal changes in cervical sympathetic nerve activity, blood pressure, heart rate, electrocardiograms and cardiac tissue structure. The P2Y12 antagonist clopidogrel improved abnormal alterations in cardiac function and tissue structure in MI rats. Short hairpin RNA (shRNA) against uc.48+ significantly inhibited P2Y12 receptor upregulation and its co-expression with glial fibrillary acidic protein (GFAP) in SCGs, and ameliorated the cardiac dysfunction in MI rats. By contrast, overexpression of uc.48+ increased the expression of P2Y12 in SCGs and enhanced cervical sympathetic nerve activity in control rats. Direct interaction between uc.48+ and the P2Y12 receptor was predicted using the bioinformatic tool CatRAPID and confirmed by RNA immunoprecipitation. Moreover, overexpression of the P2Y12 receptor reversed the protective effect of uc.48+ shRNA on cardiac dysfunction in MI rats. Uc.48 shRNA treatment also inhibited the enhanced rise of intracellular free Ca2+ level ([Ca2+]i) evoked by the P2Y12 agonist 2-methylthio-adenosine-5′-diphosphate (2-MeSADP) in SGCs of SCGs after oxygen-glucose deprivation (OGD) treatment. These data demonstrated that uc.48+ shRNA could counteract the P2Y12 upregulation and improve P2Y12-implicated cardiac dysfunction due to MI.

Review of Tuberous Breast Deformity: Developments over the Last 20 Years.

Background:Tuberous breast (TB) deformity is a condition characterized by alterations in breast morphology and tissue structure with high prevalence in the general population. The literature provides sparse descriptions of TB, as not many investigations on the condition have been conducted. The aim of this review was to analyze and provide a holistic overview on the morphological characteristics of the TB.Methods:A review of current literature was performed using the PubMed database from 2001 to 2021. The key words used for the review included “tuberous breast,” “constricted breast,” and “stenotic breast.” We included articles that analyzed the anatomic and histologic characteristics of TB.Results:From 213 articles, only 42 met the inclusion criteria. A total of 171 articles were excluded, as they were letters, not related to the condition, or were written in a foreign language. The studies in this review drew on hypothesis on the embryological origin of TB and analyzed the composition of TB tissues, consisting in a constricting fibrous ring, made of longitudinally arranged collagen and elastic fibers. Furthermore, the review reports the different anatomical and surgical classifications, as well as the various surgical corrective procedures developed throughout history up to 2021.Conclusion:The review describes all etiological, epidemiologic, anatomical, histological, and surgical characteristics of tuberous breast.

Polymorphisms in Genes Involved in Inflammation and Periodontitis: A Narrative Review.

Current evidence pinpoints that the variability in periodontitis traits in humans may be attributable to genetic factors. Different allelic variants can result in alterations in tissue structure, antibody responses and inflammatory mediators. Consequently, genetic variations may act as protective or risk factors for periodontal diseases. A number of features of the inflammatory and immune response that seem to play a role in the development of periodontitis have a clearly established genetic basis. Identifying genes that contribute to the pathogenesis of periodontitis may be utilized for risk assessment in both aggressive and chronic periodontitis. The aim of this narrative review is to summarize the role of polymorphisms in genes involved in inflammation and periodontitis, including cellular receptors, tissue compatibility antigens, antibodies and cytokines.

Optical Coherence Elastography as a Tool for Studying Deformations in Biomaterials: Spatially-Resolved Osmotic Strain Dynamics in Cartilaginous Samples.

This paper presents a recently developed variant of phase-resolved Optical Coherence Elastography (OCE) enabling non-contact visualization of transient local strains of various origins in biological tissues and other materials. In this work, we demonstrate the possibilities of this new technique for studying dynamics of osmotically-induced strains in cartilaginous tissue impregnated with optical clearing agents (OCA). For poroelastic water-containing biological tissues, application of non-isotonic OCAs, various contrast additives, as well as drug solutions administration, may excite transient spatially-inhomogeneous strain fields of high magnitude in the tissue bulk, initiating mechanical and structural alterations. The range of the strain reliably observed by OCE varied from ±10−3 to ±0.4 for diluted and pure glycerol, correspondingly. The OCE-technique used made it possible to reveal previously inaccessible details of the complex spatio-temporal evolution of alternating-sign osmotic strains at the initial stages of agent diffusion. Qualitatively different effects produced by particular hydrophilic OCAs, such as glycerol and iohexol, are discussed, as well as concentration-dependent differences. Overall, the work demonstrates the unique abilities of the new OCE-modality in providing a deeper insight in real-time kinetics of osmotically-induced strains relevant to a broad range of biomedical applications.

Phenanthrene disrupting effects on the thyroid system of Arabian seabream, Acanthopagrus arabicus: In situ and in vivo study

Phenanthrene, a polycyclic aromatic hydrocarbon (PAH), is one of the endocrine disrupting chemicals (EDCs). The present study aimed to evaluate the effects of phenanthrene on histophysiology of thyroid in Arabian seabream (Acanthopagrus arabicus). In this regards, different concentrations of phenanthrene (2, 20 and 40 pg/gbw) were injected to Acanthopagrus arabicus and changes in thyroid tissue structure and the serum levels of triiodothyronine (T3) and Thyroxine (T4) were assessed. The experiment lasted 21 days. Alterations in thyroid tissue structure and T3 and T4 serum levels also were assessed in Acanthopagrus arabicus caught from different stations of the Persian Gulf (Jafari, Samail, Arvand, Zangi, Bahrakan). In addition, the concentration of phenanthrene was measured in the fish muscle and sediment samples from the stations. Phenanthrene concentration reached the maximum level in the muscle of all injected fish after 4 days and then decreased by the end of the experiment. The highest and lowest concentrations of phenanthrene were recorded in the fish muscle and sediment samples collected from Jafari and Bahrakan, respectively. The levels of T3 and T4 decreased dose dependently in phenanthrene-injected fish up to day 7 and then increased by the end of the experiment. The serum level of T3 and T4 in fish collected from different stations was as follows: Jafari<Samail<Arvand<Zangi≤Bahrakan. Some tissue changes observed in fish included decrease in the thickness of thyroid follicle epithelium and increase in follicle diameter. In conclusion, according to the results, phenanthrene significantly affected thyroid function in fish.

Expression of Concern: Refat et al. Antioxidant, Antigenotoxic, and Hepatic Ameliorative Effects of Quercetin/Zinc Complex on Cadmium-Induced Hepatotoxicity and Alterations in Hepatic Tissue Structure. Coatings 2021, 11, 501

Following acceptance of the Special Issue article by the Guest Editor, El-Sayed Abd El-Aziz, concerns were raised regarding the integrity of the peer review process [...]

Estimation of Cole Parameters in ex-vivo tissues as a function of degradation time

Bioimpedance spectroscopy has been used to evaluate and characterize the integrity of different tissues and organs, as well as to detect tissue structural alterations. The tissue electrical model alterations as an influence of the anisotropy of the tissue structure and its intrinsic metabolism on the degradation dynamic have not been completely understood. In this work, the dynamic of Cole parameters was estimated as a function of degradation time in ex vivo skeletal muscle, skin, and white adipose tissues. The results indicate a non-linear behavior function of the Cole parameters through degradation progress in the three evaluated tissues, and such non-linearities might be associated with different capacities of adaptation to anaerobic metabolism, energy production, and water content under stress conditions.

P056 Crohn’s Disease associated fibrosis modulates the expression of collagen receptors

Abstract Background Crohn’s Disease (CD) patients often develop stenotic complications as immunomodulatory treatments do not prevent the fibrogenic response in the affected tissues, where a dysregulated activation of stromal cells provokes an excessive deposition of extracellular matrix (ECM). Recent evidences support the notion that local cells can sense the consequent alterations in tissue structure and rigidity through receptors that respond to some ECM components, and this may perpetuate the fibrogenic process even in the absence of inflammation. We aim to analyse the relevance of these signalling pathways in the fibrotic process associated to CD. Methods We obtained fibrotic ileal tissues from CD patients and healthy ileal samples from colon carcinoma patients (control), and analysed the expression (RT-PCR, IHQ) of collagen receptors (integrins, discoidin domain receptors/DDR) and of markers for some stromal cells (fibroblasts, endothelial cells). The relationship between these sets of data was analysed by Pearson’s correlation and the results organized as a correlation matrix. The expression of collagen receptors was also analysed in endothelial cells (HUVEC) treated with TGFβ 2 (1ng/ml, 48h). Results Ileal samples from CD patients present a differential gene expression of collagen receptors (Fig 1), with increased levels of ITGA10, ITGA11 and DDR2, and reduced expression of DDR1. In CD tissues, the expression of ITGA11 and DDR1 showed a significant correlation, positive and negative respectively, with that of endothelial markers (Fig 2). These correlations do not occur in control tissues. Integrin-α11 was detected in endothelial cells of submucosal vessels (IHQ). In HUVEC, TGFβ 2 increased the expression of ITGA11 (8.1±0.7 fold induction, p&amp;lt;0.01) and reduced that of DDR1 (0.74±0.06 fold induction, p&amp;lt;0.01), without affecting that of the other collagen receptors. Conclusion Intestinal tissues from CD patients affected by fibrosis present an altered pattern of expression of collagen receptors, which suggests a regulatory role of the ECM in the fibrotic response, while the correlation analysis and the changes induced by the fibrotic cytokine TGFβ in endothelial cells insinuates a particular relevance of these stromal cells in this process.