Transforming growth factor-β (TGF-β) is a profibrotic cytokine found in chronic renal diseases, which initiates and modulates a variety of pathophysiological processes. It is synthesized by many renal cell types and exerts its biological functions through a variety of signalling pathways, including the Smad and MAPK pathways. In renal diseases, TGF-β is upregulated and induces renal cells to produce extracellular matrix proteins leading to glomerulosclerosis as well as tubulointerstitial fibrosis. Different types of renal cells undergo different pathophysiological changes induced by TGF-β, leading to apoptosis, hypertrophy and abnormalities of podocyte foot processes, which ultimately result in renal dysfunction. In this review, we describe the effects of TGF-β on different renal cell types and the means by which TGF-β participates in the pathomechanisms of glomerular and tubulointerstitial diseases.
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http://dx.doi.org/10.1093/ndt/gft267 | DOI Listing |
Inflammopharmacology
January 2025
Department of Clinical Pharmacy, Faculty of Pharmacy, Tanta University, El-Gharbia Government, Tanta, Egypt.
Objective: This study aimed to assess the potential antifibrotic impact of zinc sulfate in chronic Hepatitis C Virus (HCV) patients receiving direct-acting antiviral therapy.
Methods: This randomized controlled study included 50 chronic HCV-infected patients with fibrosis stage (F1 & F2). Participants were randomly assigned to two groups: Group 1 (Control group, n = 25) received standard direct-acting antiviral therapy for 3 months, while Group 2 (Zinc group, n = 25) received 50 mg/day of zinc sulfate in addition to the standard direct-acting antiviral therapy for the same duration.
Nat Commun
January 2025
Zhejiang Key Laboratory of Pancreatic Disease, The First Affiliated Hospital, Zhejiang Key Laboratory of Frontier Medical Research on Cancer Metabolism, Institute of Translational Medicine, Zhejiang University School of Medicine, Hangzhou, China.
Liver fibrosis is a critical liver disease that can progress to more severe manifestations, such as cirrhosis, yet no effective targeted therapies are available. Here, we identify that ATF4, a master transcription factor in ER stress response, promotes liver fibrosis by facilitating a stress response-independent epigenetic program in hepatic stellate cells (HSCs). Unlike its canonical role in regulating UPR genes during ER stress, ATF4 activates epithelial-mesenchymal transition (EMT) gene transcription under fibrogenic conditions.
View Article and Find Full Text PDFAlthough sex determination is a fundamental process in vertebrate development, it is very plastic. Diverse genes became major sex determinants in teleost fishes. Deciphering how individual sex-determining genes orchestrate sex determination can reveal new actors in sexual development.
View Article and Find Full Text PDFBiochim Biophys Acta Mol Basis Dis
January 2025
Department of Pediatric Nephrology and Rheumatism and Immunology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong 250021, China; Department of Pediatric Nephrology and Rheumatism and Immunology, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong 250021, China. Electronic address:
Renal interstitial fibrosis is the main factor determining chronic kidney disease (CKD) progression, and renal tubular epithelial cells are the key drivers of this pathological process. Herein, we revealed significantly increased ubiquitin-specific peptidase 10 (USP10) expression in the kidney tissues of both patients with CKD and mice induced by unilateral ureteral obstruction, as well as in transforming growth factor-beta 1 (TGFβ1)-induced renal tubular epithelial cells. In vivo, treatment with the USP10 small molecule inhibitor Spautin-1, which inhibits its deubiquitinating activity, weakened renal interstitial fibrosis progression and alleviated the subsequent inflammatory response and oxidative stress in male mice.
View Article and Find Full Text PDFProc Natl Acad Sci U S A
January 2025
Key Laboratory of Molecular Nanostructure and Nanotechnology, Research/Education Center for Excellence in Molecular Sciences, Institute of Chemistry, Chinese Academy of Sciences, Beijing 100190, China.
Emerging evidence indicates that intratumor bacteria exist as an active and specific tumor component in many tumor types beyond digestive and respiratory tumors. However, the biological impact and responsible molecules of such local bacteria-tumor direct interaction on cancer therapeutic response remain poorly understood. Trastuzumab is among the most commonly used drugs targeting the receptor tyrosine-protein kinase erbB-2 (ErbB2) in breast cancer, but its resistance is inevitable, severely limiting its clinical effectiveness.
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