Colonic Epithelial Surfactant Protein D Expression Correlates with Inflammation in Clinical Colonic Inflammatory Bowel Disease

Nexøe, Anders Bathum; Pilecki, Bartosz; Huth, Sebastian von; Husby, Steffen; Pedersen, Andreas Arnholdt; Detlefsen, Sönke; Marcussen, Niels; Møeller, Jesper Bonnet; Holmskov, Uffe; Sørensen, Grith Lykke

doi:10.1093/ibd/izz009

Cited by 7 publications

(5 citation statements)

References 38 publications

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“…In a recent study by Sarashina-Kida et al (108), it was shown that SP-D could also originate from the gallbladder, where it had an anti-inflammatory role in a dextran sulfate sodium (DSS)-induced murine colitis. However, Nexoe et al (109) performed a similar study and could not replicate the anti-inflammatory role of SP-D in the DSS-model. Regardless, the conclusion is that SP-D not only originates from the lung but can be secreted by various sources, such as the arteries and gallbladder.…”

Section: Discussionmentioning

confidence: 95%

The Dual Role of Surfactant Protein-D in Vascular Inflammation and Development of Cardiovascular Disease

2019

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Cardiovascular disease (CVD) is responsible for 31% of all global deaths. Atherosclerosis is the major cause of cardiovascular disease and is a chronic inflammatory disorder in the arteries. Atherosclerosis is characterized by the accumulation of cholesterol, extracellular matrix, and immune cells in the vascular wall. Recently, the collectin surfactant protein-D (SP-D), an important regulator of the pulmonary immune response, was found to be expressed in the vasculature. Several in vitro studies have examined the role of SP-D in the vascular inflammation leading to atherosclerosis. These studies show that SP-D plays a dual role in the development of atherosclerosis. In general, SP-D shows anti-inflammatory properties, and dampens local inflammation in the vessel, as well as systemic inflammation. However, SP-D can also exert a pro-inflammatory role, as it stimulates C-C chemokine receptor 2 inflammatory blood monocytes to secrete tumor necrosis-factor α and increases secretion of interferon-γ from natural killer cells. In vivo studies examining the role of SP-D in the development of atherosclerosis agree that SP-D plays a proatherogenic role, with SP-D knockout mice having smaller atherosclerotic plaque areas, which might be caused by a decreased systemic inflammation. Clinical studies examining the association between SP-D and cardiovascular disease have reported a positive association between circulatory SP-D level, carotid intima-media thickness, and coronary artery calcification. Other studies have found that circulatory SP-D is correlated with increased risk of both total and cardiovascular disease mortality. Both in vitro, in vivo, and clinical studies examining the relationship between SP-D and CVDs will be discussed in this review.

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Section: Discussionmentioning

confidence: 95%

The Dual Role of Surfactant Protein-D in Vascular Inflammation and Development of Cardiovascular Disease

2019

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“…Some potential evidence has carried out the link between SFTPD and phylum Proteobacteria . Nexoe et al, found a strong positive correlation between inflammatory activity and expression of SFTPD in the intestinal epithelium from Inflammatory Bowel Disease (IBD) patients [ 44 ], while the increase of Proteobacteria is one of the most consistent observations in IBD individuals [ 45 ].…”

Section: Discussionmentioning

confidence: 99%

Transcriptome-wide association study identified candidate genes associated with gut microbiota

et al. 2021

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Background Gut microbiota is closely associated with host health and disease occurrence. Host genetic factor plays an important role in shaping gut microbial communities. The specific mechanism of host-regulated gene expression affecting gut microbiota has not been elucidated yet. Here we conducted a transcriptome-wide association study (TWAS) for gut microbiota by leveraging expression imputation from large-scale GWAS data sets. Results TWAS detected multiple tissue-specific candidate genes for gut microbiota, such as FUT2 for genus Bifidobacterium in transverse colon (PPERM.ANL = 1.68 × 10–3) and SFTPD for an unclassified genus of Proteobacteria in transverse colon (PPERM.ANL = 5.69 × 10–3). Fine mapping replicated 3 candidate genes in TWAS, such as HELLS for Streptococcus (PIP = 0.685) in sigmoid colon, ANO7 for Erysipelotrichaceae (PIP = 0.449) in sigmoid colon. Functional analyses detected 94 significant GO terms and 11 pathways for various taxa in total, such as GO_NUCLEOSIDE_DIPHOSPHATASE_ACTIVITY for Butyrivibrio (FDR P = 1.30 × 10–4), KEGG_RENIN_ANGIOTENSIN_SYSTEM for Anaerostipes (FDR P = 3.16 × 10–2). Literature search results showed 12 genes prioritized by TWAS were associated with 12 diseases. For instance, SFTPD for an unclassified genus of Proteobacteria was related to atherosclerosis, and FUT2 for Bifidobacterium was associated with Crohn’s disease. Conclusions Our study results provided novel insights for understanding the genetic mechanism of gut microbiota, and attempted to provide clues for revealing the influence of genetic factors on gut microbiota for the occurrence and development of diseases.

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“…The stainings were performed in parallel with validation controls using CHO cells expressing recombinant full-length FIBCD1 ( 13 ) and representative non-cancerous human colon specimens using an optimized protocol described previously ( 12 ). The semiquantitative immune score for FIBCD1 expression was performed on specimens obtained from 35 patients clinically diagnosed with CRC stage I (n=8), II (n=19), and III (n=8) using a scoring system consisting of a distribution score and an intensity score, as described previously ( 21 ). The FIBCD1 positive epithelial cell distribution was scored from 0 to 4 as follows: 0, less than 10% of the epithelial cells were positive for FIBCD1; 1, 10%–30% of the epithelial cells were positive for FIBCD1; 2, 31%–60%, 3, 61-90%, and 4, >90% of the epithelial cells were positive for FIBCD1.…”

Section: Methodsmentioning

confidence: 99%

Expression of FIBCD1 by intestinal epithelial cells alleviates inflammation-driven tumorigenesis in a mouse model of colorectal cancer

Shahgoli,

Dubik,

Pilecki

et al. 2023

Front. Oncol.

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BackgroundColorectal cancer (CRC) ranks as the third most prevalent cancer globally, highlighting the pressing need to address its development. Inflammation plays a crucial role in augmenting the risk of CRC and actively contributes to all stages of tumorigenesis. Consequently, targeting early inflammatory responses in the intestinal tract to restore homeostasis holds significant potential for preventing and treating CRC. Fibrinogen C domain-containing 1 (FIBCD1), a chitin-binding transmembrane protein predominantly found on human intestinal epithelial cells (IECs), has garnered attention in previous research for its ability to effectively suppress inflammatory responses and promote tissue homeostasis at mucosal barriers.MethodsIn this study, we investigated the role of FIBCD1 in CRC development using transgenic mice that mimic human expression of FIBCD1 at the intestinal mucosal barrier. To model aspects of CRC, we employed the azoxymethane/dextran sodium sulfate (AOM/DSS) mouse model. Additionally, we examined the expression pattern of FIBCD1 in surgical specimens obtained from human CRC patients by immunohistochemical methods. By accessing public data repositories, we further evaluated FIBCD1 expression in colon adenocarcinoma and explored survival outcomes associated with FIBCD1 expression.ResultsHere, we demonstrate that FIBCD1 substantially impacts CRC development by significantly reducing intestinal inflammation and suppressing colorectal tumorigenesis in mice. Furthermore, we identify a soluble variant of FIBCD1 that is significantly increased in feces during acute inflammation. Finally, we demonstrate increased expression of FIBCD1 by immunohistochemistry in human CRC specimens at more developed tumor stages. These results are further supported by bioinformatic analyses of publicly available repositories, indicating increased FIBCD1 expression in tumor tissues, where higher expression is associated with unfavorable prognosis.ConclusionCollectively, these findings suggest that FIBCD1 influences early inflammatory responses in the AOM/DSS model, leading to a reduction in tumor size and burden. The increased expression of FIBCD1 in human CRC samples raises intriguing questions regarding its role in CRC, positioning it as a compelling candidate and novel molecular target for future research.

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Colonic Epithelial Surfactant Protein D Expression Correlates with Inflammation in Clinical Colonic Inflammatory Bowel Disease

Cited by 7 publications

References 38 publications

The Dual Role of Surfactant Protein-D in Vascular Inflammation and Development of Cardiovascular Disease

The Dual Role of Surfactant Protein-D in Vascular Inflammation and Development of Cardiovascular Disease

Transcriptome-wide association study identified candidate genes associated with gut microbiota

Expression of FIBCD1 by intestinal epithelial cells alleviates inflammation-driven tumorigenesis in a mouse model of colorectal cancer

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