Protective effects of L‐arginine on the intestinal epithelial barrier under heat stress conditions in rats and IEC‐6 cell line

The aim of this study was to investigate the protective effects of TGF-β1 on intestinal epithelial barrier, as well as canonical Smad and MAPK signal pathways involved in these protection processes by a IPEC-J2 model stimulated with TNF-α. IPEC-J2 monolayers were treated without or with TNF-α in the absence or presence of TGF-β1. The results showed that TGF-β1 pretreatment ameliorated TNF-α-induced intestinal epithelial barrier disturbances as indicated by decrease of transepithelial electrical resistance (TER) and increase of paracellular permeability. TGF-β1 also dramatically alleviated TNF-α-induced alteration of TJ proteins ZO-1 and occludin. Moreover, TGF-β1 pretreatment increased TβRII protein expression in IPEC-J2 monolayers challenged with TNF-α. In addition, a significant increase of Smad4 and Smad7 mRNA was also observed in the TGF-β1 pretreatment after TNF-α challenge compared with the control group. Furthermore, TGF-β1 pretreatment enhanced smad2 protein activation. These results indicated that the canonical Smad signaling pathway was activated by TGF-β1 pretreatment. Finally, TGF-β1 pretreatment decreased the ratios of the phosphorylated to total JNK and p38 (p-JNK/JNK and p-p38/p38) and increased the ratio of ERK (p-ERK/ERK). Anti-TGF-β1 Abs reduced these TGF-β1 effects. These results indicated that TGF-β1 protects intestinal integrity and influences Smad and MAPK signal pathways in IPEC-J2 after TNF-α challenge.

Download Full-text

Su1780 Eicosapentaenoic Acid Enhances Heat Stress-Impaired Intestinal Epithelial Barrier Function in Caco-2 Cells

Gastroenterology ◽

10.1016/s0016-5085(13)61757-6 ◽

2013 ◽

Vol 144 (5) ◽

pp. S-475

Author(s):

Gui-Zhen Xiao ◽

Li-Qun Tang ◽

Fang-Fang Yuan ◽

Zhi-Feng Liu ◽

Ya-Li Zhang ◽

...

Keyword(s):

Heat Stress ◽

Eicosapentaenoic Acid ◽

Barrier Function ◽

Epithelial Barrier ◽

Intestinal Epithelial ◽

Intestinal Epithelial Barrier ◽

Epithelial Barrier Function

Download Full-text

Intestinal epithelial barrier function and tight junction proteins with heat and exercise

Journal of Applied Physiology ◽

10.1152/japplphysiol.00536.2015 ◽

2016 ◽

Vol 120 (6) ◽

pp. 692-701 ◽

Cited By ~ 88

Author(s):

Karol Dokladny ◽

Micah N. Zuhl ◽

Pope L. Moseley

Keyword(s):

Heat Stress ◽

Tight Junction ◽

Barrier Function ◽

Epithelial Barrier ◽

Intestinal Epithelial ◽

Tight Junction Proteins ◽

Intestinal Epithelial Barrier ◽

Epithelial Tight Junction ◽

Junction Proteins

A single layer of enterocytes and tight junctions (intercellular multiprotein complexes) form the intestinal epithelial barrier that controls transport of molecules through transcellular and paracellular pathways. A dysfunctional or “leaky” intestinal tight junction barrier allows augmented permeation of luminal antigens, endotoxins, and bacteria into the blood stream. Various substances and conditions have been shown to affect the maintenance of the intestinal epithelial tight junction barrier. The primary focus of the present review is to analyze the effects of exertional or nonexertional (passive hyperthermia) heat stress on tight junction barrier function in in vitro and in vivo (animals and humans) models. Our secondary focus is to review changes in tight junction proteins in response to exercise or hyperthermic conditions. Finally, we discuss some pharmacological or nutritional interventions that may affect the cellular mechanisms involved in maintaining homeostasis of the intestinal epithelial tight junction barrier during heat stress or exercise.

Download Full-text

Intestinal Epithelial Barrier Maturation by Enteric Glial Cells Is GDNF-Dependent

International Journal of Molecular Sciences ◽

10.3390/ijms22041887 ◽

2021 ◽

Vol 22 (4) ◽

pp. 1887

Author(s):

Michael Meir ◽

Felix Kannapin ◽

Markus Diefenbacher ◽

Yalda Ghoreishi ◽

Catherine Kollmann ◽

...

Keyword(s):

Glial Cells ◽

Primary Cultures ◽

Epithelial Barrier ◽

Protective Effects ◽

Intestinal Epithelial ◽

Intestinal Epithelial Barrier ◽

Caco2 Cells ◽

Enteric Glial Cells

Enteric glial cells (EGCs) of the enteric nervous system are critically involved in the maintenance of intestinal epithelial barrier function (IEB). The underlying mechanisms remain undefined. Glial cell line-derived neurotrophic factor (GDNF) contributes to IEB maturation and may therefore be the predominant mediator of this process by EGCs. Using GFAPcre x Ai14floxed mice to isolate EGCs by Fluorescence-activated cell sorting (FACS), we confirmed that they synthesize GDNF in vivo as well as in primary cultures demonstrating that EGCs are a rich source of GDNF in vivo and in vitro. Co-culture of EGCs with Caco2 cells resulted in IEB maturation which was abrogated when GDNF was either depleted from EGC supernatants, or knocked down in EGCs or when the GDNF receptor RET was blocked. Further, TNFα-induced loss of IEB function in Caco2 cells and in organoids was attenuated by EGC supernatants or by recombinant GDNF. These barrier-protective effects were blunted when using supernatants from GDNF-deficient EGCs or by RET receptor blockade. Together, our data show that EGCs produce GDNF to maintain IEB function in vitro through the RET receptor.

Download Full-text

The glial cell-line derived neurotrophic factor: a novel regulator of intestinal barrier function in health and disease

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.00125.2016 ◽

2016 ◽

Vol 310 (11) ◽

pp. G1118-G1123 ◽

Cited By ~ 11

Author(s):

Michael Meir ◽

Sven Flemming ◽

Natalie Burkard ◽

Johanna Wagner ◽

Christoph-Thomas Germer ◽

...

Keyword(s):

Cell Line ◽

Glial Cell ◽

Neurotrophic Factor ◽

Intestinal Barrier ◽

Chronic Inflammatory Bowel Disease ◽

Epithelial Barrier ◽

Intestinal Epithelial ◽

Intestinal Epithelial Barrier ◽

Health And Disease ◽

Inflammatory Bowel

Regulation of the intestinal epithelial barrier is a differentiated process, which is profoundly deranged in inflammatory bowel diseases. Recent data provide evidence that the glial cell line-derived neurotrophic factor (GDNF) is critically involved in intestinal epithelial wound healing and barrier maturation and exerts antiapoptotic effects under certain conditions. Furthermore, not only the enteric nervous system, but also enterocytes synthesize GDNF in significant amounts, which points to a potential para- or autocrine signaling loop between enterocytes. Apart from direct effects of GDNF on enterocytes, an immunomodulatory role of this protein has been previously assumed because of a significant reduction of inflammation in a model of chronic inflammatory bowel disease after application of GDNF. In this review we summarize the current knowledge of GDNF on intestinal epithelial barrier regulation and discuss the novel role for GDNF as a regulator of intestinal barrier functions in health and disease.

Download Full-text