IL-1β Impacts Vascular Integrity and Lymphatic Function in the Embryonic Omentum

2022 ◽  
Author(s):  
Matthew Menendez ◽  
Anna Drozd ◽  
Katarzyna Borawska ◽  
Joanna J Chmielewska ◽  
Meng-Ling Wu ◽  
...  
Keyword(s):  
Blood Vessels ◽  
Developmental Process ◽  
Imaging Techniques ◽  
Interleukin 1 ◽  
Lymphatic Vessels ◽  
Cell Types ◽  
Interacting Protein ◽  
Vascular Integrity ◽  
Trigger Receptor ◽  
Lymphatic Development

Background: The chromatin remodeling enzyme Brahma Related Gene 1 (BRG1) regulates gene expression in a variety of rapidly differentiating cells during embryonic development. However, the critical genes that BRG1 regulates during lymphatic vascular development are unknown. Methods: We used genetic and imaging techniques to define the role of BRG1 in murine embryonic lymphatic development, although this approach inadvertently expanded our study to multiple interacting cell types. Results: We found that omental macrophages fine-tune an unexpected developmental process by which erythrocytes escaping from naturally discontinuous omental blood vessels are collected by nearby lymphatic vessels. Our data indicate that circulating fibrin(ogen) leaking from gaps in omental blood vessels can trigger inflammasome-mediated interleukin 1 beta (IL-1β) production and secretion from nearby macrophages. IL-1β destabilizes adherens junctions in omental blood and lymphatic vessels, contributing to both extravasation of erythrocytes and their uptake by lymphatics. BRG1 regulates IL-1β production in omental macrophages by transcriptionally suppressing the inflammasome trigger Receptor Interacting Protein Kinase 3 (RIPK3). Conclusions: Genetic deletion of Brg1 in embryonic macrophages leads to excessive IL-1β production, erythrocyte leakage from blood vessels, and blood-filled lymphatics in the developing omentum. Altogether, these results highlight a novel context for epigenetically-regulated crosstalk between macrophages, blood vessels, and lymphatics.

scholarly journals Dual function of perivascular fibroblasts in vascular stabilization in zebrafish

PLoS Genetics ◽  
2020 ◽  
Vol 16 (10) ◽  
pp. e1008800
Author(s):  
Arsheen M. Rajan ◽  
Roger C. Ma ◽  
Katrinka M. Kocha ◽  
Dan J. Zhang ◽  
Peng Huang
Keyword(s):  
Blood Vessels ◽  
Time Lapse ◽  
Cell Types ◽  
Dual Function ◽  
Dual Roles ◽  
Vascular Integrity ◽  
Genetic Ablation ◽  
Mural Cells ◽  
And Function ◽  
Time Lapse Imaging

Blood vessels are vital to sustain life in all vertebrates. While it is known that mural cells (pericytes and smooth muscle cells) regulate vascular integrity, the contribution of other cell types to vascular stabilization has been largely unexplored. Using zebrafish, we identified sclerotome-derived perivascular fibroblasts as a novel population of blood vessel associated cells. In contrast to pericytes, perivascular fibroblasts emerge early during development, express the extracellular matrix (ECM) genes col1a2 and col5a1, and display distinct morphology and distribution. Time-lapse imaging reveals that perivascular fibroblasts serve as pericyte precursors. Genetic ablation of perivascular fibroblasts markedly reduces collagen deposition around endothelial cells, resulting in dysmorphic blood vessels with variable diameters. Strikingly, col5a1 mutants show spontaneous hemorrhage, and the penetrance of the phenotype is strongly enhanced by the additional loss of col1a2. Together, our work reveals dual roles of perivascular fibroblasts in vascular stabilization where they establish the ECM around nascent vessels and function as pericyte progenitors.

scholarly journals Spatial organization of endometrial gene expression at the onset of embryo attachment in pigs

BMC Genomics ◽  
2019 ◽  
Vol 20 (1) ◽  
Author(s):  
Shuqin Zeng ◽  
Susanne E. Ulbrich ◽  
Stefan Bauersachs
Keyword(s):  
Gene Expression ◽  
Blood Vessels ◽  
Growth Regulation ◽  
Spatial Organization ◽  
Interleukin 1 ◽  
Differential Expression Analysis ◽  
Cell Types ◽  
Cell Junction ◽  
Endometrial Cell ◽  
Filamentous Form

Abstract Background During the preimplantation phase in the pig, the conceptus trophoblast elongates into a filamentous form and secretes estrogens, interleukin 1 beta 2, interferons, and other signaling molecules before attaching to the uterine epithelium. The processes in the uterine endometrium in response to conceptus signaling are complex. Thus, the objective of this study was to characterize transcriptome changes in porcine endometrium during the time of conceptus attachment considering the specific localization in different endometrial cell types. Results Low-input RNA-sequencing was conducted for the main endometrial compartments, luminal epithelium (LE), glandular epithelium (GE), blood vessels (BV), and stroma. Samples were isolated from endometria collected on Day 14 of pregnancy and the estrous cycle (each group n = 4) by laser capture microdissection. The expression of 12,000, 11,903, 11,094, and 11,933 genes was detectable in LE, GE, BV, and stroma, respectively. Differential expression analysis was performed between the pregnant and cyclic group for each cell type as well as for a corresponding dataset for complete endometrium tissue samples. The highest number of differentially expressed genes (DEGs) was found for LE (1410) compared to GE, BV, and stroma (800, 1216, and 384). For the complete tissue, 3262 DEGs were obtained. The DEGs were assigned to Gene Ontology (GO) terms to find overrepresented functional categories and pathways specific for the individual endometrial compartments. GO classification revealed that DEGs in LE were involved in ‘biosynthetic processes’, ‘related to ion transport’, and ‘apoptotic processes’, whereas ‘cell migration’, ‘cell growth’, ‘signaling’, and ‘metabolic/biosynthetic processes’ categories were enriched for GE. For blood vessels, categories such as ‘focal adhesion’, ‘actin cytoskeleton’, ‘cell junction’, ‘cell differentiation and development’ were found as overrepresented, while for stromal samples, most DEGs were assigned to ‘extracellular matrix’, ‘gap junction’, and ‘ER to Golgi vesicles’. Conclusions The localization of differential gene expression to different endometrial cell types provided a significantly improved view on the regulation of biological processes involved in conceptus implantation, such as the control of uterine fluid secretion, trophoblast attachment, growth regulation by Wnt signaling and other signaling pathways, as well as the modulation of the maternal immune system.

Role of inflammation in the development of colorectal cancer

2020 ◽  
Vol 20 ◽  
Author(s):  
Sridhar Muthusami ◽  
R. Ileng Kumaran ◽  
Kokelavani Nampalli Babu ◽  
Sneha Krishnamoorthy ◽  
Akash Guruswamy ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Chronic Inflammation ◽  
Interleukin 1 ◽  
Cell Types ◽  
Model Systems ◽  
Cytokine Gene Expression ◽  
Necrosis Factor Alpha ◽  
Tnf Α ◽  
Proinflammatory Molecules

: Chronic inflammation can lead to the development of many diseases including cancer. Inflammatory bowel disease (IBD) that includes both ulcerative colitis (UC) and Crohn's disease (CD) are risk factors for the development of colorectal cancer (CRC). Many cytokines produced primarily by the gut immune cells either during or in response to localized inflammation in the colon and rectum are known to stimulate the complex interactions between the different cell types in the gut environment resulting in acute inflammation. Subsequently, chronic inflammation together with genetic and epigenetic changes has been shown to lead to the development and progression of CRC. Various cell types present in the colon such as enterocytes, Paneth cells, goblet cells and macrophages express receptors for inflammatory cytokines and respond to tumor necrosis factor alpha (TNF-α), interleukin-1 beta (IL-1β), IL-6 and other cytokines. Among the several cytokines produced, TNF-α and IL-1β are the key proinflammatory molecules that play critical roles in the development of CRC. The current review is intended to consolidate the published findings to focus on the role of proinflammatory cytokines, namely TNF-α and IL-1β, on inflammation (and the altered immune response) in the gut, to better understand the development of CRC in IBD, using various experimental model systems, preclinical and clinical studies. Moreover, this review also highlights the current therapeutic strategies available (monotherapy and combination therapy), to alleviate the symptoms or treat inflammationassociated CRC by using monoclonal antibodies or aptamers to block proinflammatory molecules, inhibitors of tyrosine kinases in inflammatory signaling cascade, competitive inhibitors of proinflammatory molecules, and the nucleic acid drugs like small activating RNAs (saRNAs) or microRNA (miRNA) mimics to activate tumor suppressor or repress oncogene/proinflammatory cytokine gene expression.

scholarly journals Mesenteric Cysts: A Retrospective Review. Its Not All That Simple

2020 ◽  
Vol 154 (Supplement_1) ◽  
pp. S117-S118
Author(s):  
M Bourgeau ◽  
V Avadhani
Keyword(s):  
Cyst Wall ◽  
Imaging Techniques ◽  
Case Reports ◽  
Lymphatic Vessels ◽  
Mucinous Cystadenoma ◽  
Final Diagnosis ◽  
Cystic Mass ◽  
Pathological Examination ◽  
Urachal Cyst ◽  
Mesenteric Cysts

Abstract Introduction/Objective Mesenteric cysts are rare intra-abdominal lesions in adults. However, with the advanced imaging techniques and laparoscopic techniques, they are more often being identified and resected when clinically significant. There is a lack of detailed information in histopathology (except as case reports) since mesentery is generally neglected in our organ-based textbooks. The aim of our study is to highlight the importance of identifying and classifying mesenteric cystic lesions; they are not all that simple. Methods We performed a retrospective search on all mesenteric cysts submitted as excisions in our electronic database from 2013-2019. We classified them as per the de Perrot (PMID: 11053936) classification with modification. Results Our search showed: A. Lymphatic origin-11 (lymphangioma-10, Lymphangioma hamartomatous-1, associated with LAM-0), B. Mesothelial origin-68 (Benign mesothelial cysts-57, multilocular mesothelial cyst-11), C. Enteric origin- 3, D. Urogenital origin (Urachal cyst, mullerian inclusion cyst)-9, E. Mature cystic teratom-2, F. Pseudocyst-12, G. Epithelial cyst (not urogenital)- 11 (a/w LAMN-3, MCN-4, Mucinous cystadenoma-4), H. Associated with carcinoma-2. Case illustration: A 61-year-old male presented with worsening dysphagia, emesis and hiccups. A CT scan showed a 21.2 cm cystic mass with at least one septation (Fig 1). The cyst was resected. On gross pathological examination, the cyst measured 18 cm in greatest dimension with a thick, rough, tan-brown capsule. Microscopic examination showed a fibrous capsule, and cyst wall composed of numerous lymphatic vessels (CD31 positive) and prominent smooth muscle proliferation (Desmin positive). Scattered lymphoid aggregates were also present throughout the cyst wall. No definite epithelial lining was identified and was suspected to have been denuded. HMB-45 immunostain was negative, ruling out association with LAM. The final diagnosis of a Lymphangiomyoma, hamartomatous was rendered. Conclusion Though most of the mesenteric cysts are benign, some of them are significantly important such as Lymphangiomyoma (esp secondary to LAM), MCN, those associated with LAMN etc. and identifying and differentiating from their mimics has distinct clinical implications.

scholarly journals Mechanisms and cell lineages in lymphatic vascular development

Angiogenesis ◽  
2021 ◽  
Author(s):  
Daniyal J. Jafree ◽  
David A. Long ◽  
Peter J. Scambler ◽  
Christiana Ruhrberg
Keyword(s):  
Emerging Technologies ◽  
Vascular Development ◽  
Lymphatic Vessels ◽  
Experimental Techniques ◽  
Knowledge Gaps ◽  
Cellular Mechanisms ◽  
Cell Lineages ◽  
Lymphatic Vasculature ◽  
Lymphatic Development ◽  
Health And Disease

AbstractLymphatic vessels have critical roles in both health and disease and their study is a rapidly evolving area of vascular biology. The consensus on how the first lymphatic vessels arise in the developing embryo has recently shifted. Originally, they were thought to solely derive by sprouting from veins. Since then, several studies have uncovered novel cellular mechanisms and a diversity of contributing cell lineages in the formation of organ lymphatic vasculature. Here, we review the key mechanisms and cell lineages contributing to lymphatic development, discuss the advantages and limitations of experimental techniques used for their study and highlight remaining knowledge gaps that require urgent attention. Emerging technologies should accelerate our understanding of how lymphatic vessels develop normally and how they contribute to disease.

The Notch1-Dll4 signaling pathway regulates mouse postnatal lymphatic development

Blood ◽  
2011 ◽  
Vol 118 (7) ◽  
pp. 1989-1997 ◽  
Author(s):  
Kyle Niessen ◽  
Gu Zhang ◽  
John Brady Ridgway ◽  
Hao Chen ◽  
Ganesh Kolumam ◽  
...  
Keyword(s):  
Blood Vessel ◽  
Notch Signaling ◽  
Signaling Pathway ◽  
Lymphatic Vessels ◽  
Mouse Skin ◽  
Notch Signaling Pathway ◽  
Cell Phenotype ◽  
Mural Cell ◽  
Lymphatic Development ◽  
Vessel Development

Abstract The Notch signaling pathway plays a fundamental role during blood vessel development. Notch signaling regulates blood vessel morphogenesis by promoting arterial endothelial differentiation and pro-viding spatial and temporal control over “tip cell” phenotype during angiogenic sprouting. Components of the Notch signaling pathway have emerged as potential regulators of lymphatic development, joining the increasing examples of blood vessel regulators that are also involved in lymphatic development. However, in mammals a role for the Notch signaling pathway during lymphatic development remains to be demonstrated. In this report, we show that blockade of Notch1 and Dll4, with specific function-blocking antibodies, results in defective postnatal lymphatic development in mice. Mechanistically, Notch1-Dll4 blockade is associated with down-regulation of EphrinB2 expression, been shown to be critically involved in VEGFR3/VEGFC signaling, resulting in reduced lymphangiogenic sprouting. In addition, Notch1-Dll4 blockade leads to compromised expression of distinct lymphatic markers and to dilation of collecting lymphatic vessels with reduced and disorganized mural cell coverage. Finally, Dll4-blockade impairs wound closure and severely affects lymphangiogenesis during the wound healing in adult mouse skin. Thus, our study demonstrates for the first time in a mammalian system that Notch1-Dll4 signaling pathway regulates postnatal lymphatic development and pathologic lymphangiogenesis.

Weight loading young chicks inhibits bone elongation and promotes growth plate ossification and vascularization

2005 ◽  
Vol 98 (6) ◽  
pp. 2381-2389 ◽  
Author(s):  
A. Reich ◽  
N. Jaffe ◽  
A. Tong ◽  
I. Lavelin ◽  
O. Genina ◽  
...  
Keyword(s):  
Blood Vessels ◽  
Growth Plate ◽  
Developmental Process ◽  
Mechanical Strain ◽  
Cell Counting ◽  
Mechanical Stimuli ◽  
Growth Plates ◽  
Average Width ◽  
The Matrix ◽  
Weight Loading

The mechanical stimuli resulting from weight loading play an important role in mature bone remodeling. However, the effect of weight loading on the developmental process in young bones is less well understood. In this work, chicks were loaded with bags weighing 10% of their body weight during their rapid growth phase. The increased load reduced the length and diameter of the long bones. The average width of the bag-loaded group's growth plates was 75 ± 4% that of the controls, and the plates showed increased mineralization. Northern blot analysis, in situ hybridization, and longitudinal cell counting of mechanically loaded growth plates showed narrowed expression zones of collagen types II and X compared with controls, with no differences between the relative proportions of those areas. An increase in osteopontin (OPN) expression with loading was most pronounced at the bone-cartilage interface. This extended expression overlapped with tartarate-resistant acid phosphatase staining and with the front of the mineralized matrix in the chondro-osseous junction. Moreover, weight loading enhanced the penetration of blood vessels into the growth plates and enhanced the gene expression of the matrix metalloproteinases MMP9 and MMP13 in those growth plates. On the basis of these results, we speculate that the mechanical strain on the chondrocytes in the growth plate causes overexpression of OPN, MMP9, and MMP13. The MMPs enable penetration of the blood vessels, which carry osteoclasts and osteoblasts. OPN recruits the osteoclasts to the cartilage-bone border, thus accelerating cartilage resorption in this zone and subsequent ossification which, in turn, contributes to the observed phenotype of narrower growth plate and shorter bones.

scholarly journals Selective expression of the scaffold protein JSAP1 in spermatogonia and spermatocytes

Reproduction ◽  
2006 ◽  
Vol 131 (4) ◽  
pp. 711-719 ◽  
Author(s):  
Munkhuu Bayarsaikhan ◽  
Akiko Shiratsuchi ◽  
Davaakhuu Gantulga ◽  
Yoshinobu Nakanishi ◽  
Katsuji Yoshioka
Keyword(s):  
Protein Kinase ◽  
Western Blotting ◽  
Cell Types ◽  
Mapk Signaling ◽  
Scaffold Protein ◽  
Mitogen Activated Protein Kinase ◽  
Interacting Protein ◽  
Early Postnatal Development ◽  
Mitogen Activated Protein ◽  
Signaling Modules

Scaffold proteins of mitogen-activated protein kinase (MAPK) intracellular signal transduction pathways mediate the efficient and specific activation of the relevant MAPK signaling modules. Previously, our group and others have identified c-Jun NH2-terminal kinase (JNK)/stress-activated protein kinase-associated protein 1 (JSAP1, also known as JNK-interacting protein 3) as a scaffold protein for JNK MAPK pathways. Although JSAP1 is expressed in the testis in adults, its expression during development has not been investigated. In addition, it is unknown which types of cells in the testis express the scaffold protein. Here, we examined the expression of JSAP1 in the testis of mice aged 14 days, 20 days, 6 weeks, and 12 weeks by immunohistochemistry and Western blotting. The specificity of the anti-JSAP1 antibody was evaluated from its reactivity to exogenously expressed JSAP1 and a structurally related protein, and by antigen-absorption experiments. The immunohistochemical analyses with the specific antibody showed that the JSAP1 protein was selectively expressed in the spermatogonia and spermatocytes, but not in other cell types, including spermatids and somatic cells, during development. However, not all spermatogonia and spermatocytes were immunopositive either, especially in the 12-week-old mouse testis. Furthermore, we found by Western blotting that the expression levels of JSAP1 protein vary during development; there is high expression until 6 weeks after birth, which approximately corresponds to the end of the first wave of spermatogenesis. Collectively, these results suggest that JSAP1 function may be important in spermatogenic cells during early postnatal development.

scholarly journals Expression of mRNA for IL1 beta, IL6 and TGF beta 1 in developing human bone and cartilage.

1994 ◽  
Vol 42 (6) ◽  
pp. 733-744 ◽  
Author(s):  
R A Dodds ◽  
K Merry ◽  
A Littlewood ◽  
M Gowen
Keyword(s):  
Mrna Expression ◽  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
Close Association ◽  
Interleukin 1 ◽  
Cell Types ◽  
Tgf Beta ◽  
Specific Stage ◽  
Growth Factor Beta

Using in situ hybridization, we investigated the expression of mRNA for interleukin-1 beta (IL1 beta), interleukin-6 (IL6), and transforming growth factor-beta-1 (TGF beta 1) in sections of developing bone in human osteophytes. The expression was related to the cellular activity of alkaline phosphatase to aid in the identification of pre-osteoblast populations. IL1 beta mRNA was localized in active osteoblasts within distinct areas of intramembranous ossification. However, the expression was sporadic and appeared to occur at a specific stage of the osteoblast life cycle. There was no IL1 beta mRNA expression in any cell types during endochondral ossification. IL6 mRNA expression was located within pre-osteoblasts and in newly differentiated and matrix-secreting osteoblasts; expression was absent or reduced in flattened, inactive osteoblasts. Weak or no IL6 expression was observed in chondroblasts and chondrocytes, respectively. However, there was a close association between IL6 mRNA expression and the differentiation of mesenchymal cells into osteoblasts. TGF beta 1 expression was localized to osteoblasts apposed to bone or cartilage matrix; the intensity of expression correlated with matrix secretion. Chondroblasts and chondrocytes expressed lower but significant levels of TGF beta 1 mRNA; the expression was lost with the progression to calcifying cartilage. The three cytokines studied were differentially expressed both temporally and spatially, suggesting different roles for each in osteoblast and chondrocyte function.

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