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Calcineurin inhibitors (CNIs) are indispensable immunosuppressants for transplant recipients and patients with autoimmune diseases, but chronic use causes nephrotoxicity, including kidney fibrosis. Why inhibiting calcineurin, a serine/threonine phosphatase, causes kidney fibrosis remains unknown. We performed single-nucleus RNA sequencing of the kidney from a chronic CNI nephrotoxicity mouse model and found an increased proportion of injured proximal tubule cells, which exhibited altered expression of genes associated with oxidative phosphorylation, cellular senescence and fibrosis.
View Article and Find Full Text PDFThe human intestine plays a pivotal role in nutrient absorption and immune system regulation. Along the longitudinal axis, cell-type composition changes to meet the varying functional requirements. Therefore, our protocol focuses on the processing of the whole human intestine to facilitate the analysis of region-specific characteristics such as tissue architecture and changes in cell populations.
View Article and Find Full Text PDFWnt3a Enhances Mesenchymal Stem Cell Engraftment and Differentiation in a Chronic Obstructive Pulmonary Disease Rat Model.
Int J Chron Obstruct Pulmon Dis
January 2025
Department of Respiratory and Critical Care Medicine, Jiangxi Provincial Key Laboratory of Respiratory Diseases, Jiangxi Institute of Respiratory Diseases, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi, 330006, People's Republic of China.
Background: Bone marrow mesenchymal stem cell (BMSC) therapy is a novel approach for treating COPD. However, the difficulty in engraftment and easy clearance of BMSCs in vivo has hindered their clinical application. Hence, exploring effective methods to improve the engraftment and differentiation rates of BMSCs in vivo is urgent.
View Article and Find Full Text PDFHigh BMP7 Expression May Worsen Airway Disease in COPD by Altering Epithelial Cell Behavior.
Int J Chron Obstruct Pulmon Dis
January 2025
Department of Obstetrics and Gynecology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, People's Republic of China.
Purpose: Airway disease is the main pathological basis of chronic obstructive pulmonary disease (COPD), but the underlying mechanisms are unknown. Bone morphogenetic protein-7 (BMP7) is a multi-functional growth factor that belongs to the transforming growth factor superfamily, which affects the regulation of proliferation, differentiation, and apoptosis. Previous research has shown that BMP7 is highly expressed in the airway epithelia of patients with COPD, but its role in airway disease has not been fully elucidated.
View Article and Find Full Text PDFThis study describes a complex human in vitro model for evaluating anti-inflammatory drug response in the alveoli that may contribute to the reduction of animal testing in the pre-clinical stage of drug development. The model is based on the human alveolar epithelial cell line Arlo co-cultured with macrophages differentiated from the THP-1 cell line, creating a physiological biological microenvironment. To mimic the three-dimensional architecture and dynamic expansion and relaxation of the air-blood-barrier, they are grown on a stretchable microphysiological lung-on-chip.
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