scholarly journals Role of TGF-Beta and Smad7 in Gut Inflammation, Fibrosis and Cancer

Biomolecules ◽  
2020 ◽  
Vol 11 (1) ◽  
pp. 17
Author(s):  
Carmine Stolfi ◽  
Edoardo Troncone ◽  
Irene Marafini ◽  
Giovanni Monteleone
Keyword(s):  
Transforming Growth Factor ◽  
Cell Types ◽  
Mucosal Immune Response ◽  
The Body ◽  
Mucosal Cell ◽  
Gut Inflammation ◽  
Bowel Diseases ◽  
Inflammatory Bowel ◽  
Tgf Β1

The human gastrointestinal tract contains the largest population of immune cells in the body and this is a reflection of the fact that it is continuously exposed to a myriad of dietary and bacterial antigens. Although these cells produce a variety of inflammatory cytokines that could potentially promote tissue damage, in normal conditions the mucosal immune response is tightly controlled by counter-regulatory factors, which help induce and maintain gut homeostasis and tolerance. One such factor is transforming growth factor (TGF)-β1, a cytokine produced by multiple lineages of leukocytes, stromal cells and epithelial cells, and virtually targets all the gut mucosal cell types. Indeed, studies in animals and humans have shown that defects in TGF-β1 production and/or signaling can lead to the development of immune-inflammatory pathologies, fibrosis and cancer in the gut. Here, we review and discuss the available evidence about the role of TGF-β1 and Smad7, an inhibitor of TGF-β1 activity, in gut inflammation, fibrosis and cancer with particular regard to the contribution of these two molecules in the pathogenesis of inflammatory bowel diseases and colon cancer.

scholarly journals Transforming growth factor β1 protein and mRNA levels in inflammatory bowel diseases: towards solving the contradictions by longitudinal assessment of the protein and mRNA amounts.

1970 ◽  
Vol 60 (4) ◽  
Author(s):  
Anna Liberek ◽  
Zbigniew Kmieć ◽  
Piotr M Wierzbicki ◽  
Joanna Jakóbkiewicz-Banecka ◽  
Tomasz Liberek ◽  
...  
Keyword(s):  
Growth Factor ◽  
Transforming Growth Factor ◽  
Transforming Growth Factor Β1 ◽  
Mrna Levels ◽  
Longitudinal Assessment ◽  
Active Stage ◽  
Intestinal Tissue ◽  
Bowel Diseases ◽  
Inflammatory Bowel ◽  
Tgf Β1

Previously published studies on levels of the transforming growth factor-β1 (TGF-β1) protein and mRNA of the corresponding gene in patients suffering from inflammatory bowel diseases (IBD) gave varying results, leading to contradictory conclusions. To solve the contradictions, we aimed to assess longitudinally TGF-β1 protein and mRNA levels at different stages of the disease in children suffering from IBD. The study group consisted of 19 pediatric patients with IBD at the age between 3.5 and 18.4 years. The control group consisted of 42 children aged between 2.0 and 18.0 years. The plasma TGF-β1 concentration was measured with ELISA. mRNA levels of the TGF-β1 gene isolated from samples of the intestinal tissue were assessed by reverse transcription and real-time PCR. Levels of TGF-β1 protein in plasma and corresponding mRNA in intestinal tissue were significantly higher in IBD patients than in controls. TGF-β1 and corresponding transcripts were also more abundant in plasma and intestinal tissue, respectively, in patients at the active stage of the disease than during remission. In every single IBD patient, plasma TGF-β1 level and mRNA level in intestinal tissue was higher at the active stage of the disease than during remission. Levels of TGF-β1 and corresponding mRNA are elevated during the active stage of IBD but not during the remission. Longitudinal assessment of this cytokine in a single patient may help to monitor the clinical course of IBD.

scholarly journals Involvement of Smad7 in Inflammatory Diseases of the Gut and Colon Cancer

2021 ◽  
Vol 22 (8) ◽  
pp. 3922
Author(s):  
Edoardo Troncone ◽  
Irene Marafini ◽  
Carmine Stolfi ◽  
Giovanni Monteleone
Keyword(s):  
Transforming Growth Factor ◽  
Intestinal Inflammation ◽  
Inflammatory Responses ◽  
Inflammatory Diseases ◽  
Cell Types ◽  
Transforming Growth Factor Β1 ◽  
Cancer Prognosis ◽  
Refractory Celiac Disease ◽  
Bowel Diseases ◽  
Tgf Β1

In physiological conditions, the human intestinal mucosa is massively infiltrated with various subsets of immune cells, the activity of which is tightly regulated by several counter-regulatory factors. One of these factors is transforming growth factor-β1 (TGF-β1), a cytokine produced by multiple cell types and targeting virtually all the intestinal mucosal cells. Binding of TGF-β1 to its receptors triggers Smad2/3 signaling, thus culminating in the attenuation/suppression of immune–inflammatory responses. In patients with Crohn’s disease and patients with ulcerative colitis, the major human inflammatory bowel diseases (IBD), and in mice with IBD-like colitis, there is defective TGF-β1/Smad signaling due to high levels of the intracellular inhibitor Smad7. Pharmacological inhibition of Smad7 restores TGF-β1 function, thereby reducing inflammatory pathways in patients with IBD and colitic mice. On the other hand, transgenic over-expression of Smad7 in T cells exacerbates colitis in various mouse models of IBD. Smad7 is also over-expressed in other inflammatory disorders of the gut, such as refractory celiac disease, necrotizing enterocolitis and cytomegalovirus-induced colitis, even though evidence is still scarce and mainly descriptive. Furthermore, Smad7 has been involved in colon carcinogenesis through complex and heterogeneous mechanisms, and Smad7 polymorphisms could influence cancer prognosis. In this article, we review the data about the expression and role of Smad7 in intestinal inflammation and cancer.

The role of macrophages in inflammatory bowel diseases

2009 ◽  
Vol 11 ◽  
Author(s):  
Sigrid E.M. Heinsbroek ◽  
Siamon Gordon
Keyword(s):  
Inflammatory Bowel Diseases ◽  
Inflammatory Responses ◽  
Intestinal Flora ◽  
The Body ◽  
Intestinal Immunity ◽  
Bowel Diseases ◽  
Inflammatory Bowel ◽  
Intestinal Macrophage ◽  
Small And Large Intestine

The small and large intestine contain the largest number of macrophages in the body and these cells are strategically located directly underneath the epithelial layer, enabling them to sample the lumen. Such intestinal macrophages have a different phenotype from other tissue macrophages in that they ingest and may kill microbes but they do not mediate strong pro-inflammatory responses upon microbial recognition. These properties are essential for maintaining a healthy intestine. It is generally accepted that tolerance to the intestinal flora is lost in inflammatory bowel diseases, and genes involved in microbial recognition, killing and macrophage activation have already been associated with these diseases. In this review, we shed light on the intestinal macrophage and how it influences intestinal immunity.

scholarly journals Vitamin D Deficiency, Osteoporosis and Effect on Autoimmune Diseases and Hematopoiesis: A Review

2021 ◽  
Vol 22 (16) ◽  
pp. 8855
Author(s):  
Massimo De Martinis ◽  
Alessandro Allegra ◽  
Maria Maddalena Sirufo ◽  
Alessandro Tonacci ◽  
Giovanni Pioggia ◽  
...  
Keyword(s):  
Vitamin D ◽  
Autoimmune Diseases ◽  
Hematological Malignancies ◽  
The Body ◽  
Vitamin Supplementation ◽  
Bone Homeostasis ◽  
Bowel Diseases ◽  
Inflammatory Bowel ◽  
The Brain

Vitamin D (VD) is essential for bone homeostasis, but it is also involved in pleiotropic effects on various organs and tissues. In adults, VD deficiency can cause or exacerbate osteoporosis and induce osteomalacia. However, every tissue and cell in the body has a VD receptor, including the brain, heart, stomach, pancreas, skin, gonads, and immune cells, and a deficiency may modify the function of these organs. Thus, the wide-ranging actions of VD help to explain why a reduction in VD amount has been correlated with numerous chronic diseases. In fact, VD deficiency increases the risk of osteoporosis and several other diseases and complications characterized by impaired bone metabolisms, such as autoimmune diseases, inflammatory bowel diseases, allergy, endocrinological diseases, hematological malignancies, and bone marrow transplantation. This review aims to investigate the link between VD deficiency, osteoporosis, and its concomitant diseases. Further epidemiological and mechanistic studies are necessary in order to ascertain the real role of hypovitaminosis in causing the reported diseases; however, adequate vitamin supplementation and restoration of metabolic normality could be useful for better management of these pathologies.

The gut immune system, inflammatory bowel diseases, and the body immune homeostasis: modern treatment strategies

2016 ◽  
Vol 6 (2) ◽  
pp. 0-0 ◽  
Author(s):  
G.C. Actis
Keyword(s):  
Bacterial Species ◽  
Critical Mass ◽  
Treatment Strategies ◽  
Cell Types ◽  
The Body ◽  
Full Description ◽  
Mucosal Cell ◽  
Inflammatory Bowel ◽  
Signaling Receptors ◽  
Autoreactive Cells

The digestive tract is nowadays conceived as a barrier organ constituted by a mucosal membrane separating the gut lumen from the inner milieu. The gut lumen is laden by a myriad of antigens brought about by the diet, but also pertaining to the overwhelming bacterial species of the gut microbiome. The mucosal cell population comprehends epithelial cells, and a variety of immune reactive cells. Of them, the mononuclear types effecting innate responses are endowed by membrane signaling receptors and, as a rule, are sensing the polysaccharides of bacterial cell walls; non-tolerated signals may then push the chain reaction on, to end in full activation of inflammation mediators. Acquired immunity is in turn mainly effected by T-cell types, some of them, behaving as autoreactive cells, may induce metastatic inflammation beyond bowel boundaries, partly explaining the so-called extra-intestinal manifestations of inflammatory bowel disease (IBD). The scenario is further complicated by the possible influence of epigenetic factors: diet, stress, smoking, drugs. Being IBD a low-penetrance disorder, for the full phenotype to develop, a critical mass of the above listed factors (typically, a disturbed membrane permeability, an immune stimulus, and an epigenetic factor) must occur. In the century since the full description of IBD, a variegated plethora of measures have been attempted. Some updated designs are now under scrutiny. Microbiota engineering, apoptosis modulation, and diet modification are just a few of the measures that we are arbitrarily describing here.

Gut Mycobiota and Fungal Metabolites in Human Homeostasis

2018 ◽  
Vol 20 (2) ◽  
pp. 232-240 ◽  
Author(s):  
Izabella Mogilnicka ◽  
Marcin Ufnal
Keyword(s):  
Wide Spectrum ◽  
Biological Effects ◽  
Fungal Species ◽  
Fungal Metabolites ◽  
Human Gut ◽  
Fecal Transplantation ◽  
Bacterial Microbiota ◽  
Bowel Diseases ◽  
Inflammatory Bowel

Background:Accumulating evidence suggests that microbiota play an important role in host’s homeostasis. Thus far, researchers have mostly focused on the role of bacterial microbiota. However, human gut is a habitat for several fungal species, which produce numerous metabolites. Furthermore, various types of food and beverages are rich in a wide spectrum of fungi and their metabolites.Methods:We searched PUBMED and Google Scholar databases to identify clinical and pre-clinical studies on fungal metabolites, composition of human mycobiota and fungal dysbiosis.Results:Fungal metabolites may serve as signaling molecules and exert significant biological effects including trophic, anti-inflammatory or antibacterial actions. Finally, research suggests an association between shifts in gut fungi composition and human health. Changes in mycobiota composition have been found in obesity, hepatitis and inflammatory bowel diseases.Conclusion:The influence of mycobiota and dietary fungi on homeostasis in mammals suggests a pharmacotherapeutic potential of modulating the mycobiota which may include treatment with probiotics and fecal transplantation. Furthermore, antibacterial action of fungi-derived molecules may be considered as a substitution for currently used antibacterial agents and preservatives in food industry.

Role of MicroRNAs in Colon Cancer Progression and Metastasis

2020 ◽  
Vol 20 ◽  
Author(s):  
Shruthi Sanjitha Sampath ◽  
Sivaramakrishnan Venkatabalsubramanian ◽  
Satish Ramalingam
Keyword(s):  
Colon Cancer ◽  
Cancer Progression ◽  
Target Genes ◽  
Tumour Progression ◽  
Intestinal Barrier ◽  
Colon Cancer Progression ◽  
Bowel Diseases ◽  
Inflammatory Bowel ◽  
Novel Therapeutic Strategies

: MicroRNAs regulate gene expression at the posttranscriptional level by binding to the mRNA of their target genes. The dysfunction of miRNAs is strongly associated with the inflammation of the colon. Besides, some microRNAs are shown to suppress tumours while others promote tumour progression and metastasis. Inflammatory bowel diseases include Crohn’s disease and Ulcerative colitis which increase the risk factor for inflammation-associated colon cancer. MicroRNAs are shown to be involved in gastrointestinal pathologies, by targeting the transcripts encoding proteins of the intestinal barrier and their regulators that are associated with inflammation and colon cancer. Detection of these microRNAs in the blood, serum, tissues, faecal matter, etc will enable us to use these microRNAs as biomarkers for early detection of the associated malignancies and design novel therapeutic strategies to overcome the same. Information on MicroRNAs can be applied for the development of targeted therapies against inflammation-mediated colon cancer.

scholarly journals The Role of Enterobacteriaceae in Gut Microbiota Dysbiosis in Inflammatory Bowel Diseases

2021 ◽  
Vol 9 (4) ◽  
pp. 697
Author(s):  
Valerio Baldelli ◽  
Franco Scaldaferri ◽  
Lorenza Putignani ◽  
Federica Del Chierico
Keyword(s):  
Inflammatory Bowel Diseases ◽  
Inflammatory Diseases ◽  
Species Level ◽  
Unknown Etiology ◽  
Gut Dysbiosis ◽  
Bowel Diseases ◽  
Inflammatory Bowel ◽  
Symbiotic Microbiota ◽  
Gut Microbiota Dysbiosis

Inflammatory bowel diseases (IBDs) are a group of chronic gastrointestinal inflammatory diseases with unknown etiology. There is a combination of well documented factors in their pathogenesis, including intestinal microbiota dysbiosis. The symbiotic microbiota plays important functions in the host, and the loss of beneficial microbes could favor the expansion of microbial pathobionts. In particular, the bloom of potentially harmful Proteobacteria, especially Enterobacteriaceae, has been described as enhancing the inflammatory response, as observed in IBDs. Herein, we seek to investigate the contribution of Enterobacteriaceae to IBD pathogenesis whilst considering the continuous expansion of the literature and data. Despite the mechanism of their expansion still remaining unclear, their expansion could be correlated with the increase in nitrate and oxygen levels in the inflamed gut and with the bile acid dysmetabolism described in IBD patients. Furthermore, in several Enterobacteriaceae studies conducted at a species level, it has been suggested that some adherent-invasive Escherichia coli (AIEC) play an important role in IBD pathogenesis. Overall, this review highlights the pivotal role played by Enterobacteriaceae in gut dysbiosis associated with IBD pathogenesis and progression.

Sign in / Sign up

Export Citation Format

Share Document