Deoxynivalenol inhibits the expression of trefoil factors (TFF) by intestinal human and porcine goblet cells

et al. 2019

Toxins

Deoxynivalenol (DON) is a potential pathogenic factor to humans and animals, and intestinal tract is the primary target organ of DON. Data concerning the effects of DON on rabbits are scarce, especially for weaning rabbits. In this study, 45 weaning rabbits (35 d) were randomly and equally assigned into three groups. Group A was fed basic diet, while groups B and C were added DON at 0.5 mg/kg BW/d and 1.5 mg/kg BW/d, respectively, based on the basic diet. The experiment lasted for 24 days and the intestinal morphology, expression, and distribution of several cytokines in intestinal segments have been examined. The results indicated that ADG decreased while F/G increased significantly compared with the control group after DON added at 1.5 mg/kg BW/d. Some of the morphometric parameters (villi length, crypt depth, and goblet cells density) changed after DON was added. Meanwhile, the concentration as well as the expression levels of relative protein and mRNA of IL-1β, IL-2, IL-6, and IL-8 increased significantly. The immunohistochemistry results illustrated that the quantity and distribution of positive cells of inflammatory cytokines were changed after DON was added. In conclusion, the addition of DON damaged the intestinal morphology and changed the distribution and expression of inflammatory cytokines. The toxic effect depended on the dosage of DON.

Section: Discussionmentioning

confidence: 61%

“…The goblet cells not only produce mucoprotein, but also secrete some factors which can make epithelial renewed and repaired [36]. However, the study on the goblet cells induced by DON was less studied.…”

Section: Discussionmentioning

confidence: 99%

The Effect of Low and High Dose Deoxynivalenol on Intestinal Morphology, Distribution, and Expression of Inflammatory Cytokines of Weaning Rabbits

Yang

Huang

et al. 2019

Toxins

“…The intestine is the initial line of defense against food contaminants and the primary target for DON [3]. A recent study has demonstrated that DON intoxicated intestinal health by depressing the expression of trefoil factors (TFFs) in goblet cells [4]. DON induced inhibition of TFFs contributes to impaired intestinal integrity through alteration of mucosal regeneration or repair [4].…”

Section: Introductionmentioning

confidence: 99%

“…A recent study has demonstrated that DON intoxicated intestinal health by depressing the expression of trefoil factors (TFFs) in goblet cells [4]. DON induced inhibition of TFFs contributes to impaired intestinal integrity through alteration of mucosal regeneration or repair [4]. Trefoil factors (TFF1, 2, and 3) are a family of protease-resistant peptides that are abundantly secreted onto the surface of the intestine by mucin-producing cells.…”

Section: Introductionmentioning

confidence: 99%

Deoxynivalenol Inhibits Porcine Intestinal Trefoil Factors Expression in Weanling Piglets and IPEC-J2 Cells

Zhang

et al. 2019

Toxins

Trefoil factors (TFFs) are regulatory peptides playing critical roles in mucosal repair and protection against a variety of insults within the gastrointestinal tract. This work aimed to explore the effects of deoxynivalenol (DON) on intestinal TFFs expression using in vivo and in vitro models. In an animal trial, twenty-four 28-d-old barrows (Duroc × Landrace × Large White; initial body weight = 7.6 ± 0.7 kg) were randomly divided into three treatments for 28 days, including a control diet (0.61 mg DON/kg feed), and two levels of DON-contaminated diets containing 1.28 and 2.89 mg DON/kg feed, respectively. Piglets exposed to DON had lower mRNA expression of TFF1, TFF2, TFF3, as well as Claudin-4 in the intestine (P < 0.05). Dietary DON exposure decreased the protein levels of TFF2 and TFF3 in the jejunum as demonstrated by western blot and immunohistochemistry. In intestinal porcine epithelial cells (IPEC-J2), DON depressed the mRNA expression of TFF2, TFF3, and Claudin-4. Overexpression of sterile alpha motif (SAM) pointed domain E26 transformation-specific (ETS) factor (SPDEF) was found to attenuate DON-induced suppression of TFFs in IPEC-J2 cells. Altogether, our work shows, for the first time, that dietary DON exposure depresses the expression of intestinal TFFs in piglets. Given the fundamental role of TFFs in intestinal mucosal homeostasis, our observations indicate that the DON content in animal feed should be strictly controlled based on the existing regulation for DON.

“…TFF3 protects and repairs the gastrointestinal mucosa, maintains the tight junction barrier integrity and restores normal intestinal permeability during inflammatory bowel disease pathogenesis (7). TFF3 is also present in the neural lobe of the porcine pituitary gland (8,9).…”

Section: Introductionmentioning

confidence: 99%

Extracellular production of recombinant sus scrofa trefoil factor 3 by Brevibacillus choshinensis

Wen

et al. 2020

Exp Ther Med

Trefoil factor 3 (TFF3) is involved in cell adhesion, motility and apoptosis, regulates mucosal immunity and maintains the functional integrity of intestinal epithelia. The upregulation of TFF3 expression in the weaning rat intestine attracted our interest. The present study hypothesized that TFF3 may serve a role in preventing diarrhea in weaning piglets, which is an important consideration in the pig farming industry. Previous recombinant TFF3 protein expression yields obtained from Escherichia coli were too low and the bioactivity of the protein was poor. Hence, this expression system was unsuitable for industrial applications. The present study explored the production of recombinant sus scrofa TFF3 in a Brevibacillus choshinensis (B. choshinensis) expression system, aiming to enhance the expression level of bioactive protein. To achieve this, the sus scrofa TFF3-encoding gene fragment was fused into an E. coli-Brevibacillus shuttle vector pNCMO2. High levels of TFF3 (30 mg/l) were produced and secreted into the B. choshinensis culture medium in soluble form with a molecular mass of 13.6 kDa and high immunoreactivity in western blotting. Thus, Brevibacillus may be used to produce useful mucosal factors for biochemical analyses and mucosal protection, and in industrial applications to produce novel inhibitors of diarrhea.