Similar Datasets
Project description:Cadmium (Cd) is a toxic heavy metal that has a significant impact on the liver and kidneys, rendering them highly susceptible to its toxic effects. However, the precise mechanism remains uncertain. Mice were exposed to Cd resulting severe ferroptosis and liver tissue damage via regulating hepatic GPX4 levels. It is noteworthy that despite the considerably lower concentration of Cd in the kidney compared to the liver, the oxidative damage observed in the exposed mice was significantly more severe in the kidney. It was therefore postulated that hepatic disorders may engage in such hepatorenal communication, thereby leading to the pathological phenotypes of distant organs under conditions of Cd exposure. The results of the mechanistic studies indicated that Cd-induced hepatocyte exosomes, which contain a variety of miRNAs produced by hepatocytes, such as miR-2137, etc., are capable of targeting renal GPX4 and reducing the level of GPX4 in renal cells. This resulted in the occurrence of ferroptosis in the kidneys. Injection of the appropriate dosage of Cd-induced exosomes, derived from hepatocytes, is sufficient to induce kidney damage in vivo. Our data support the hypothesis that treatment with an antagomir targeting miR-2137 is capable of inhibiting this process. Moreover, our findings revealed that selenium (Se) supplementation was sufficient to protect against Cd-induced hepatic and renal toxicity by elevating the expression level of selenoprotein GPX4 in vivo. In conclusion, we have identified liver-derived exosomes and their implications for hepatorenal communication under Cd exposure. This provides a new target for understanding the mechanism of Cd-induced hepatorenal communication. Our findings indicate that exosomes may serve as biomarkers and potential therapeutic agents for the exposure of Cd toxicity.
2025-07-17 | GSE302882 | GEO
Project description:In this study, we investigated miRNA expression profiles in ileal mucosa from CD patients in different settings (post-operative recurrent (POR) CD, newly diagnosed CD and late stage CD)) and controls.
2019-03-01 | GSE102127 | GEO
Project description:Proper development of surface epithelium (SE) is a requisite for the normal development and function of ectodermal appendages; however, the molecular mechanisms underlying SE commitment remain largely unexplored. Here, we developed a KRT8 reporter system and utilized it to identify FOXO4 and SP6 as novel, essential regulators governing SE commitment. We found that the FOXO4-SP6 axis governs SE fate and its abrogation markedly impedes SE fate determination. Mechanistically, FOXO4 regulates SE initiation by shaping the SE chromatin accessibility landscape and regulating the deposition of H3K4me3. SP6, as a novel effector of FOXO4, activated SE-specific genes through modulating the H3K27ac deposition across their super enhancers. Our work highlights the regulatory function of the FOXO4-SP6 axis in SE development, contributing to an improved understanding of SE fate decisions and providing a research foundation for the therapeutic application of ectodermal dysplasia.
2025-05-22 | GSE280746 | GEO
Project description:Proper development of surface epithelium (SE) is a requisite for the normal development and function of ectodermal appendages; however, the molecular mechanisms underlying SE commitment remain largely unexplored. Here, we developed a KRT8 reporter system and utilized it to identify FOXO4 and SP6 as novel, essential regulators governing SE commitment. We found that the FOXO4-SP6 axis governs SE fate and its abrogation markedly impedes SE fate determination. Mechanistically, FOXO4 regulates SE initiation by shaping the SE chromatin accessibility landscape and regulating the deposition of H3K4me3. SP6, as a novel effector of FOXO4, activated SE-specific genes through modulating the H3K27ac deposition across their super enhancers. Our work highlights the regulatory function of the FOXO4-SP6 axis in SE development, contributing to an improved understanding of SE fate decisions and providing a research foundation for the therapeutic application of ectodermal dysplasia.
2025-05-22 | GSE280745 | GEO
Project description:Background: The molecular pathogenesis of small intestinal adenocarcinomas (SBA) is not well understood. Defining its molecular pathogenesis may lead us to better clinical interventions. Aim: to identify the molecular changes characteristic of SBA. Methods: Forty-eight SBA (thirty-three non coeliac disease (CD)-related and 15 CD-related) were characterized for chromosomal aberrations, by high resolution array comparative hybridization (aCGH), microsatellite status (MSI) and APC promoter methylation and mutation status. Furthermore, molecular alterations found in CD-related SBA were compared to non-CD related SBA. Results: Chromosomal changes were observed in 77% of the SBA. The most frequently (>10%) DNA copy number changes found were gains on 5p15.33-5p12, 7p22.3-7q11.21, 7q21.2-7q21.3, 7q22.1-7q34, 7q36.1, 7q36.3, 8q11.21-8q24.3, 9q34.11-9q34.3, 13q11-13q34, 16p13.3, 16p11.2, 19q13.2 and 20p13-20q13.33 and losses of 4p13-4q35.2, 5q15-5q21.1 and 21p11.2-21q22.11. Seven highly amplified regions on 6p21.1, 7q21.1, 8p23.1, 11p13, 16p11.2, 17q12-q21.1 and 19q13.2 were also identified. CD-related and non CD-related SBA displayed similar chromosomal aberrations. Promoter hypermethylation of the APC gene was found in 48% non CD-related and 73% CD-related SBA. No nonsense mutations were found. Last, 10% of the non CD-related SBA were MSI, whereas 43% of the CD-related SBA were MSI. Conclusions: Our study characterized specific chromosomal aberrations and amplifications involved in SBA pathogenesis. At the chromosomal level, CD-related and non CD-related SBA do not differ. The involvement of the MMR system in the pathogenesis of the CD-related SBA was larger than what has been observed in no CD-related SBA. No nonsense mutations were found in SBA, but frequent promoter methylation in CD-related SBA.
2009-10-07 | GSE15470 | GEO