Ochratoxin A (OTA) is a mycotoxin that induces fibrosis and epithelial-to-mesenchymal transitions (EMT) in kidneys and livers. It enters our bodies through food consumption, where it is absorbed in the intestines. However, the impact of OTA on the intestines is yet to be studied. MicroRNA (miRNAs) are small non-coding single-stranded RNAs that block the transcription of specific mRNAs and are, therefore, involved in many biochemical processes. Our findings indicate that OTA can induce EMT and intestinal fibrosis both in vivo and in vitro. This study examines the impact of OTA on intestinal toxicity and the role of miRNAs in this process. Following OTA treatment, miR-155-5p was the most elevated miRNA by next-generation sequencing. Our research showed that OTA increased miR-155-5p levels through transforming growth factor β (TGF-β), leading to the development of intestinal fibrosis and EMT. Additionally, the study identified that the modulation of TGF-β and miR-155-5p by OTA is linked to the inhibition of CCAAT/enhancer-binding protein β (C/EBPβ) and Smad2/3 accumulation in the progression of intestinal fibrosis.
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http://dx.doi.org/10.3390/toxins15070473 | DOI Listing |
Am J Physiol Cell Physiol
December 2024
Department of Nephrology, the First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Chinese Medicine), Hangzhou, Zhejiang, 310000, China.
Intestinal microbiota are pathophysiologically involved in diabetic nephropathy (DN). Dapagliflozin, recognized for its blood glucose-lowering effect, has demonstrated efficacy in improving DN. However, the mechanisms beyond glycemic control that mediate the impact of dapagliflozin on DN remain unclear.
View Article and Find Full Text PDFAdv Sci (Weinh)
December 2024
State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing, Jiangsu, 210023, China.
Intestinal fibrosis, a severe complication of Crohn's disease (CD), is linked to chronic inflammation, but the precise mechanism by which immune-driven intestinal inflammation leads to fibrosis development is not fully understood. This study investigates the role of myeloid-derived suppressor cells (MDSCs) in intestinal fibrosis in CD patients and a 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced mouse model. Elevated MDSCs are observed in inflamed intestinal tissues prior to fibrosis and their sustained presence in fibrotic tissues of both CD patients and murine models.
View Article and Find Full Text PDFJ Biomed Mater Res B Appl Biomater
January 2025
Department of Biomedical Engineering, TOBB Economy and Technology University, Ankara, Türkiye.
Despite the variety of proposed solutions, anastomotic leakage is still a critical complication after colorectal surgery, which causes increased clinical mortality and morbidity. By enhancing microcirculation in the colonic mucosa, the use of Iloprost (Ilo) has shown promising results for the healing of anastomosis. The purpose of this study is to examine the performance of Ilo-impregnated Polycaprolactone:Gelatin electrospun membranes (PCL/Gel/Ilo) on anastomosis repair and intra-abdominal adhesion behavior in the Rat colon.
View Article and Find Full Text PDFFront Med (Lausanne)
December 2024
Department of Nephrology, Urology & Nephrology Center, Zhejiang Provincial People's Hospital (Affiliated People's Hospital, Hangzhou Medical College), Hangzhou, China.
Diabetic nephropathy is an important complication of diabetic microvascular injury, and it is also an important cause of end-stage renal disease. Its high prevalence and disability rate significantly impacts patients' quality of life while imposing substantial social and economic burdens. Gut microbiota affects host metabolism, multiple organ functions, and regulates host health throughout the life cycle.
View Article and Find Full Text PDFeGastroenterology
October 2024
Department of Medicine, Indiana University School of Medicine, Indianapolis, Indiana, USA.
Alcohol-associated liver disease (ALD) is a growing global health concern and its prevalence and severity are increasing steadily. While bacterial endotoxin translocation into the portal circulation is a well-established key factor, recent evidence highlights the critical role of sterile inflammation, triggered by diverse stimuli, in alcohol-induced liver injury. This review provides a comprehensive analysis of the complex interactions within the hepatic microenvironment in ALD.
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