Advanced IgA nephropathy with impaired renal function benefits from losartan treatment in rats

Wang, Hao; Fu, Wei; Jin, Zhouhui; Wang, Yunman; Yao, Weiguo; Yin, Peihao; Peng, Wen

doi:10.3109/0886022x.2013.794686

Cited by 6 publications

(6 citation statements)

References 18 publications

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“…During week 6, the mice were intravenously administered 0.2 ml of 2 mmol/L phosphate buffer containing 0.1% BSA once daily for three consecutive days. At week 8, the mice were administered staphylococcal enterotoxin (SEB, 10503027, Thermo Fisher Scientific, Waltham, MA, United States) via tail vein injection once weekly for 3 weeks at increasing doses of 0.5 mg/kg, 0.6 mg/kg, and 0.8 mg/kg ( Jia et al, 2007 ; He et al, 2010 ; Wang, Fu et al, 2013 ), during weeks 8, 9, and 10, respectively. After SEB injection at week 8, surviving model mice were divided into four groups of six mice each.…”

Section: Methodsmentioning

confidence: 99%

Liuwei Dihuang Pills Inhibit Podocyte Injury and Alleviate IgA Nephropathy by Directly Altering Mesangial Cell-Derived Exosome Function and Secretion

et al. 2022

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Background: Immunoglobulin A nephropathy (IgAN) is the most common glomerular disease worldwide. Its pathological features include IgA immune complex deposition, accompanied by mesangial cell proliferation and mesangial matrix expansion. This study was conducted to investigate the effects of Liuwei Dihuang pills (LWDHW) on IgAN in mice and human podocytes, as well as to determine their underlying mechanisms of action.Methods: For in vitro experiments, podocytes were exposed to the human mesangial cell culture medium supernatant of glomerular cells treated with aggregated IgA1 (aIgA1) and LWDHW-containing serum. Cell viability and the proportion of positive cells were evaluated using CCK-8 and flow apoptosis kits, respectively. The cells were collected for western blot analysis. Twenty-four mice with IgAN induced by oral bovine serum albumin administration combined with tail vein injection of staphylococcal enterotoxin B were randomly divided into four groups of six mice each: untreated model group, model + LWDHW group, model + rapamycin group, and model + LWDHW + rapamycin group. The normal control group contained six mice. The red blood cell count in the urine, urine protein, blood urea nitrogen, serum creatinine, and IgA deposition were determined, and TUNEL and western blotting were performed in the mouse kidney tissues.Results:In vitro experiments showed that LWDHW promoted autophagy by regulating the PI3K/Akt/mTOR signalling pathway and improved the damage to podocytes caused by the aIgA1-treated mesangial cell supernatant. This study demonstrates the effectiveness of LWDHW for treating IgAN. In the animal experiments, LWDHW significantly reduced the urine red blood cell count, serum creatinine and urea nitrogen contents, and 24 h urinary protein function and improved IgA deposition in the kidney tissues, glomerular volume, glomerular cell proliferation and polysaccharide deposition, and glomerular cell apoptosis. The pills also reversed the changes in the LC3II/I ratio and p62 content in the kidney tissues. The combination of LWDHW and rapamycin showed stronger inhibitory effects compared to those of LWDHW or rapamycin alone.Conclusion: LWDHW may improve regulation of the PI3K-Akt-mTOR pathway and inhibit autophagy in podocytes, as well as alleviate IgA nephropathy by directly altering mesangial cell exosomes.

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Section: Methodsmentioning

confidence: 99%

Liuwei Dihuang Pills Inhibit Podocyte Injury and Alleviate IgA Nephropathy by Directly Altering Mesangial Cell-Derived Exosome Function and Secretion

et al. 2022

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“…In rats treated with candesartan for 12 weeks, UAE decreased, as did TGF-β, fibronectin (FN), and RAAS components. Wang et al (2013) investigated the therapeutic role of ARB in an IgA nephropathy rat model and found that administration of losartan decreased urinary protein levels and reduced serum BUN, Scr, TGF-β1, FN, α-SMA, and FGF-1, finally delaying the progression of advanced IgA nephropathy with impaired renal function. In the IDTN and RENAAL trials, ARB treatment reduced the relative risk of reaching the primary composite end point-death, doubling of serum creatinine, or end-stage renal disease-in people with type 2 diabetes with kidney involvement by 20 and 16%, respectively (Lewis et al 2001;Brenner et al 2001).…”

Section: Angiotensin Receptor Blockers (Arbs)mentioning

confidence: 99%

Antifibrotic Roles of RAAS Blockers: Update

Zhang

Chen

2019

Advances in Experimental Medicine and Biology

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The rennin-angiotensin-aldosterone system (RAAS) has been well documented in regulating blood pressure, fluid volume, and sodium balance. Overactivity of RAAS promotes both systemic and regional glomerular capillary hypertension, which could induce hemodynamic injury to the glomerulus, leading to kidney damage and renal fibrosis via profibrotic and proinflammatory pathway. Therefore, the use of RAAS inhibitors (i.e., ACEIs, ARBs, and MRAs) as the optional therapy has been demonstrated to prevent proteinuria, and kidney fibrosis and slow the decline of renal function effectively in the process of kidney disease during the last few decades. Recently, several new components of the RAAS have been discovered, including ACE2 and the corresponding ACE2/Ang (1-7)/Mas axis, which are also present in the kidney. Besides the classic RAAS inhibitors target the angiotensin-AT1-aldosterone axis, with the expanding knowledge about RAAS, a number of potential therapeutic targets in this system is emerging. Newer agents that are more specific are being developed. The present chapter outlines the insights of the RAAS agents (classic RAAS antagonists/the new RAAS drugs), and discusses its clinical application in the combat of renal fibrosis.

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“…Many drugs used in clinical practice have anti-retrofibrotic effects, such as ACEI, ARB, aldosterone inhibitors, statins, endothelin receptors, beta-blockers, acetylsalicylic acid, metformin, and MMP inhibitors (Brewster and Perazella, 2004;Kanbay et al, 2009;Manns et al, 2012;Böhm et al, 2017;Rangarajan et al, 2018;Zhang et al, 2020), Among them, ACEI and ARB are the first-line drugs for the clinical treatment of CKD (KDOQI, 2012;Chen et al, 2018). The antifibrotic effect of ACEI/ARB may also arise from the preventive effect on glomerular injury induced by aldosterone or high intra-glomerular pressure (Obata et al, 1997;Wang et al, 2013). Although these drugs have shown some improvement in fibrosis, their therapeutic targets do not focus on fibrosis.…”

Section: Introductionmentioning

confidence: 99%

Transcriptome-Based Network Analysis Reveals Hirudin Potentiates Anti-Renal Fibrosis Efficacy in UUO Rats

Lin

Yang

et al. 2021

Front. Pharmacol.

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Background: Hirudin has been widely used in the treatment of antifibrosis. Previous studies have shown that hirudin can effectively improve the clinical remission rate of chronic kidney disease. However, the mechanism of its renal protection has not been systematically investigated.Methods: In this study, the reliability of UUO-induced renal interstitial fibrosis was evaluated by histopathological verification. High-throughput transcriptome sequencing was used to elucidate the molecular mechanism of hirudin, differentially expressed mRNAs were identified, and their functions were analyzed by GO analysis and GSEA. In addition, the RNA-seq results were validated by in vitro and vivo experiments.Results: We found 322 identical differential expressed genes (IDEs) in the UUO hirudin-treated group compared with the sham group. Functional enrichment analysis indicated that cellular amino acid metabolic processes were the most obvious enrichment pathways in biological processes. In terms of molecular functional enrichment analysis, IDEs were mainly enriched in coenzyme binding, pyridoxal phosphate binding and other pathways. In addition, microbody is the most obvious pathway for cellular components. A total of 115 signaling pathways were enriched, and AMPK, JAK-STAT, and PI3K-Akt signaling pathways were the important signaling pathways enriched. We found that PI3K, p-Akt, and mTOR expression were significantly reduced by hirudin treatment. In particular, our results showed that hirudin could induce a decrease in the expression of autophagy-related proteins such as P62, LC3, Beclin-1 in TGF-β1-induced NRK-52E cells.Conclusion: Our results suggest that hirudin may protect the kidney by ameliorating renal autophagy impairment through modulating the PI3K/Akt pathway.

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Advanced IgA nephropathy with impaired renal function benefits from losartan treatment in rats

Cited by 6 publications

References 18 publications

Liuwei Dihuang Pills Inhibit Podocyte Injury and Alleviate IgA Nephropathy by Directly Altering Mesangial Cell-Derived Exosome Function and Secretion

Liuwei Dihuang Pills Inhibit Podocyte Injury and Alleviate IgA Nephropathy by Directly Altering Mesangial Cell-Derived Exosome Function and Secretion

Antifibrotic Roles of RAAS Blockers: Update

Transcriptome-Based Network Analysis Reveals Hirudin Potentiates Anti-Renal Fibrosis Efficacy in UUO Rats

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