Aquaporin-2 in the early stages of the adenine-induced chronic kidney disease model

PLoS ONE, Journal Year: 2025, Volume and Issue: 20(1), P. e0314827 - e0314827

Published: Jan. 30, 2025

Chronic kidney disease (CKD) is one of the leading health problems in world. It silent early stages and gradually progresses, inducing renal physiological structural alterations. Moreover, CKD associated with impaired life quality, increased risk for cardiovascular diseases, reduced expectancy. Different animal models differ underlying etiology, time onset, diseases. The 0.25% adenine diet induces progressive damage, constituting an adequate model mimicking human CKD. Vasopressin (VP) was postulated as a mediator CKD, mainly acting through its V2 receptors. However, molecular mechanisms involved pathogenesis this condition progression still are not entirely understood. This study aimed to evaluate if AQP2 expression altered adenine-induced rats at development (two weeks) assess potential beneficial effect Tolvaptan (a receptor antagonist) treatment. We showed medullary two weeks administration. increase cytoplasmic, explaining urinary volume suggesting possible non-canonical role AQP2. In addition, effectively inhibited both control rats, decreasing increasing diuresis. slightly BUN plasma creatinine. On other hand, alterations induced by were prevented Tolvaptan.

Language: Английский

Inhibiting Myostatin Expression by the Antisense Oligonucleotides Improves Muscle Wasting in a Chronic Kidney Disease Mouse Model

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(7), P. 3098 - 3098

Published: March 27, 2025

Sarcopenia, a serious consequence of chronic kidney disease (CKD), is driven by elevated myostatin (MSTN), key inhibitor muscle growth. This study explored the potential an MSTN-specific antisense oligonucleotide (ASO) in reversing CKD-induced wasting mouse model. Thirty-two male C57BL/6J mice were randomly assigned to non-CKD group (n = 8, regular diet) and CKD 24, adenine diet). was induced using 0.2% adenine-supplemented diet for 4 weeks. Following this, sub-grouped into (saline, n 8), + Low-Dose ASO (25 mg/kg ASO, High-Dose (50 8). administered via subcutaneous injections 8 Muscle mass, treadmill performance, grip strength, fiber morphology assessed alongside qPCR Western blot analysis MSTN, atrogin-1, MuRF-1 expression. therapy significantly enhanced mass function enlarged fibers while effectively downregulating degradation markers. These improvements occurred without compromising renal function, as confirmed BUN, creatinine, weight, histological analysis. first demonstrate efficacy mitigating sarcopenia, offering promising targeted gene with significant clinical implications improving nutritional status physical performance CKD.

Language: Английский

Establishment and optimization of a novel mouse model of hyperuricemic nephropathy

Renal Failure, Journal Year: 2024, Volume and Issue: 46(2)

Published: Nov. 14, 2024

Hyperuricemia is a metabolic disorder characterized by elevated serum uric acid levels. Soluble urate can activate immune responses, and the excessive accumulation of in kidneys results hyperuricemic nephropathy (HN). However, lack an established HN model major obstacle to advancing research into pathogenesis development novel drugs. In this study, we generated evaluated optimized mouse combined administration potassium oxonate hypoxanthine at various dosages. Our demonstrated that intraperitoneal injection 200 mg/kg with gavage 500 caused renal injury mice, as evidenced elevation acid, creatinine, 24 h albuminuria levels, well pathological changes histology. Intraperitoneal markedly increased production inhibited uricase activity, disrupted transporters. This led supersaturated deposition kidneys, triggering inflammation fibrosis, thereby promoting progression. conclusion, successfully stable efficient mimic HN. may facilitate discovery therapeutic targets new drugs for treatment

Language: Английский