PAR2‐mediated cellular senescence promotes inflammation and fibrosis in aging and chronic kidney disease

Aging Cell, Год журнала: 2024, Номер 23(8)

Опубликована: Апрель 30, 2024

Cellular senescence contributes to inflammatory kidney disease via the secretion of and profibrotic factors. Protease-activating receptor 2 (PAR2) is a key regulator inflammation in diseases. However, relationship between PAR2 cellular has not yet been described. In this study, we found that PAR2-mediated metabolic changes renal tubular epithelial cells induced increased responses. Using an aging injury model, expression was shown be associated with senescence. Under vitro conditions NRK52E cells, activation induces cell senescent showed defective fatty acid oxidation (FAO). Cpt1α inhibition similar phenotype implicating important role FAO Finally, subjected mice lacking injury. PAR2-deficient kidneys are protected from adenine- cisplatin-induced fibrosis injury, respectively, by reducing inflammation. Moreover, exhibited reduced numbers during aging. These findings offer fresh insights into mechanisms underlying indicate targeting or may promising therapeutic approach for managing

Язык: Английский

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The Many Faces of Protease-Activated Receptor 2 in Kidney Injury

Biomedicines, Год журнала: 2025, Номер 13(2), С. 414 - 414

Опубликована: Фев. 8, 2025

Protease-activated receptor 2 (PAR2) is a seven-transmembrane, G-protein-coupled that activated by coagulation proteases such as factor VIIa and Xa other serine proteases. It potential therapeutic target for kidney injury, it enhances inflammatory fibrotic responses via the nuclear factor-kappa B mitogen-activated protein kinase cascades. The body of knowledge regarding role PAR2 in disease currently growing, its various models, acute renal fibrosis, diabetic disease, aging, thrombotic microangiopathy, has been reported. Here, we review literature to better understand aspects disease.

Язык: Английский

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p16INK4a Deletion Alleviated Obesity‐Associated Kidney Fibrosis by Regulating Metabolic Reprogramming and the Inflammasome Pathway

Journal of Cellular and Molecular Medicine, Год журнала: 2025, Номер 29(5)

Опубликована: Март 1, 2025

ABSTRACT Recent research has revealed a close association between obesity and various metabolic disorders, including renal diseases, but the mechanism is still unknown. This study explored role of p16INK4a in obesity‐related kidney fibrosis evaluated its potential as therapeutic target. Using wild‐type (WT) mice p16 KO mice, we fed both groups high‐fat diet (HFD) for 6 months. Our results showed that an HFD led to significant weight gain increased expression WT mouse kidneys. Notably, presented reduced fibrosis, indicated by decreased levels profibrotic proteins (α‐SMA collagen I) improved histological outcomes, glomeruli tubules. P16 also suppressed several proinflammatory biomarkers (MMP1, MMP3, IL‐1β, TNF‐α IL‐6) inhibited NLRP3 inflammasome pathway. The administration ABT263 further validated these findings decreasing inflammation HFD‐fed suggesting contributes fibrotic inflammatory processes. Metabolomic analyses knockout influenced pathways, linoleic acid pyrimidine metabolism, HFD‐induced Additionally, over‐expression was observed kidneys chronic disease patients with long‐term hyperlipidaemia. These highlight critical obesity‐induced damage suggest targeting may be promising approach treating inflammation.

Язык: Английский

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Molecular mechanisms of andrographolide-induced kidney injury and senescence via SIRT3 inhibition

Toxicology and Applied Pharmacology, Год журнала: 2025, Номер unknown, С. 117306 - 117306

Опубликована: Март 1, 2025

Язык: Английский

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Effects of high-fat diet on folic acid-induced kidney injury in mice

Biochimica et Biophysica Acta (BBA) - Molecular Cell Research, Год журнала: 2024, Номер 1871(8), С. 119856 - 119856

Опубликована: Сен. 30, 2024

Язык: Английский

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