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Methionine adenosyltransferase 2 A (MAT2A) and MAT2B are essential for hepatic stellate cells (HSCs) activation. Forkhead box M1 (FOXM1) transgenic mice develop liver inflammation and fibrosis. Here we examine if they crosstalk in male mice. We found FOXM1/MAT2A/2B are upregulated after bile duct ligation (BDL) and carbon tetrachloride (CCl) treatment in hepatocytes, HSCs and Kupffer cells (KCs). FDI-6, a FOXM1 inhibitor, attenuates the development and reverses the progression of CCl-induced fibrosis while lowering the expression of FOXM1/MAT2A/2B, which exert reciprocal positive regulation on each other transcriptionally. Knocking down any of them lowers HSCs and KCs activation. Deletion of FOXM1 in hepatocytes, HSCs, and KCs protects from BDL-mediated inflammation and fibrosis comparably. Interestingly, HSCs from Foxm1, hepatocytes from Foxm1, and HSCs and hepatocytes from Foxm1 have lower FOXM1/MAT2A/2B after BDL. This may be partly due to transfer of extracellular vesicles between different cell types. Altogether, FOXM1/MAT2A/MAT2B axis drives liver inflammation and fibrosis.
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http://dx.doi.org/10.1038/s41467-024-52527-8 | DOI Listing |
Am J Physiol Cell Physiol
September 2025
Division of Gastroenterology & Hepatology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Chronic diarrhea is a frequent gastrointestinal complication in both type 1 (T1D) and type 2 diabetes (T2D), although the underlying mechanisms differ: T1D is linked to autonomic neuropathy and disrupted transporter regulation, while T2D is often linked to medications and intestinal inflammation. Using streptozotocin-induced mouse models of T1D and T2D, we observed increased luminal fluid in the small intestine of both. Given the role of Na⁺/H⁺ exchanger 3 (NHE3) in fluid absorption and its loss in most diarrheal diseases, we examined NHE3 expression across intestinal segments.
View Article and Find Full Text PDFMol Cell Biochem
September 2025
Peking University Third Hospital, Beijing, China.
Cardiovascular-Kidney-Metabolic (CKM) syndrome, a newly defined systemic disorder, is characterized by the pathological interplay among diabetes, chronic kidney disease (CKD), and cardiovascular disease (CVD). Recent studies have identified chronic inflammation not only as a central mediator in the pathological progression of CKM syndrome but also as a pivotal molecular hub that drives coordinated damage across multiple organ systems. Mechanistic investigations have revealed that aberrant activation of signaling pathways such as NF-κB, Wnt, PI3K-AKT, JAK-STAT, and PPAR constitutes a complex inflammatory regulatory network.
View Article and Find Full Text PDFFunct Integr Genomics
September 2025
Department of Plastic Surgery, the First Affiliated Hospital of Fujian Medical University, Fuzhou, 350005, China.
Keloid scarring and Metabolic Syndrome (MS) are distinct conditions marked by chronic inflammation and tissue dysregulation, suggesting shared pathogenic mechanisms. Identifying common regulatory genes could unveil novel therapeutic targets. Methods.
View Article and Find Full Text PDFRev Med Suisse
August 2025
Service de gastroentérologie et d'hépatologie, Département de médecine, Hôpitaux universitaires de Genève, 1211 Genève 14.
The treatment of metabolic dysfunction-associated steatotic liver disease involves physical activity, weight loss, and management of comorbidities (diabetes, hypertension, dyslipidemia). In 2024, the American Food and Drug Administration provisionally approved resmetirom for metabolic dysfunction-associated steatohepatitis. Other promising molecules are being evaluated (glucagon-like peptide 1 receptor agonists, fibroblast growth factor 21 agonist).
View Article and Find Full Text PDFNeuropathol Appl Neurobiol
October 2025
Division of Rheumatology and Systemic Inflammatory Diseases, III. Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
Aims: Sarcoid myopathy (SaM) is characterised by granulomatous myositis (GM) and can overlap with inclusion body myositis (IBM), a late-onset chronic idiopathic inflammatory myopathy with a still enigmatic pathogenesis. As GM can occur in different clinical contexts, we aimed to examine the histomorphologic features and gene expression profiles in cases of definite SaM that may inform diagnostic and therapeutic considerations.
Methods: We performed a multidimensional characterisation of muscle biopsy specimens from patients with 'pure SaM' (n=17), SaM with concomitant IBM (SaM-IBM) (n=2), including histopathologic and ultrastructural analysis in addition to quantitative real-time polymerase chain reaction.