1‐Hydroxypyrene mediates renal fibrosis through aryl hydrocarbon receptor signalling pathway

Miao, Hua; Wu, Xia-Qing; Wang, Yanni; Chen, Dan-Qian; Lin, Changyong; Vaziri, Nosratola D.; Zhuang, Songlin; Guo, Yan; Wei, Su; Ma, Shixing; Zhang, Huanqiao; Shang, You-Quan; Yu, Xiao; Yanlong, Zhao; Mao, Jiarong; Gao, Ming; Zhang, Jinhua; Zhao, Jin; Zhang, Yuan; Zhang, Li; Yan, Zhao; Cao, Gang

doi:10.1111/bph.15705

Cited by 37 publications

(23 citation statements)

References 71 publications

(124 reference statements)

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“…In CKD patients, similar findings have been reported, where succinate and fumarate levels were negatively and positively associated with the eGFR, respectively [53]. In addition, we found the abundance of several amino acids (i.e., phenylalanine, leucine, glycine, proline, arginine) to be significantly linked to one-year eGFR, in accordance with reports from other groups in CKD patients and in animal models of CKD [54][55][56][57][58]. Lastly, spermine abundance was associated with a better outcome.…”

Section: Discussionsupporting

confidence: 91%

Estimated Renal Metabolomics at Reperfusion Predicts One-Year Kidney Graft Function

et al. 2022

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Renal transplantation is the gold-standard procedure for end-stage renal disease patients, improving quality of life and life expectancy. Despite continuous advancement in the management of post-transplant complications, progress is still needed to increase the graft lifespan. Early identification of patients at risk of rapid graft failure is critical to optimize their management and slow the progression of the disease. In 42 kidney grafts undergoing protocol biopsies at reperfusion, we estimated the renal metabolome from RNAseq data. The estimated metabolites’ abundance was further used to predict the renal function within the first year of transplantation through a random forest machine learning algorithm. Using repeated K-fold cross-validation we first built and then tuned our model on a training dataset. The optimal model accurately predicted the one-year eGFR, with an out-of-bag root mean square root error (RMSE) that was 11.8 ± 7.2 mL/min/1.73 m2. The performance was similar in the test dataset, with a RMSE of 12.2 ± 3.2 mL/min/1.73 m2. This model outperformed classic statistical models. Reperfusion renal metabolome may be used to predict renal function one year after allograft kidney recipients.

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Section: Discussionsupporting

confidence: 91%

Estimated Renal Metabolomics at Reperfusion Predicts One-Year Kidney Graft Function

et al. 2022

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“…The progression of CKD and renal fibrosis, one of the biggest issues in nephrology, indicated that patients inevitably progress ESRD and require dialysis or kidney transplantation ( Webster et al, 2017 ; Aydin et al, 2019 ; Van Sandwijk et al, 2019 ). Numerous studies have demonstrated that renal fibrosis was associated with the dysbiosis or dysregulation of gut microbiota, non-coding RNAs, renin–angiotensin system, aryl hydrocarbon receptor, IƙB/NF-ƙB, Keap1/Nrf2, TGF-β/Smad, and Wnt/β-catenin signaling pathways ( Ma et al, 2018a ; Chen et al, 2019b ; Garg and Maurya, 2019 ; Zhao et al, 2019 ; Hu et al, 2020a ; Miao et al, 2021b ; Wang et al, 2021d ; Wu et al, 2021 ; Zhou et al, 2021 ) as well as metabolite disorders including tryptophan metabolism and lipid metabolism ( Zhao, 2013a ; Zhao et al, 2015 ; Wang et al, 2019 ; Liu et al, 2021a ). Further studies have demonstrated that activation of IƙB/NF-ƙB and Keap1/Nrf2 signaling pathways could mediate or crosstalk these signaling pathways in both patients with CKD and experimental research studies ( Chen et al, 2017a ; Chen et al, 2017b ; Chen et al, 2019c ).…”

Section: Discussionmentioning

confidence: 99%

Shenkang Injection and Its Three Anthraquinones Ameliorates Renal Fibrosis by Simultaneous Targeting IƙB/NF-ƙB and Keap1/Nrf2 Signaling Pathways

Luo

Suo²,

Ren³

et al. 2021

Front. Pharmacol.

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Oxidative stress and inflammation are important and critical mediators in the development and progression of chronic kidney disease (CKD) and its complications. Shenkang injection (SKI) has been widely used to treat patients with CKD. Although the anti-oxidative and anti-inflammatory activity was involved in SKI against CKD, its bioactive components and underlying mechanism remain enigmatic. A rat model of adenine-induced chronic renal failure (CRF) is associated with, and largely driven by, oxidative stress and inflammation. Hence, we identified the anti-oxidative and anti-inflammatory components of SKI and further revealed their underlying mechanism in the adenine-induced CRF rats. Compared with control rats, the levels of creatinine, urea, uric acid, total cholesterol, triglyceride, and low-density lipoprotein cholesterol in serum were significantly increased in the adenine-induced CRF rats. However, treatment with SKI and its three anthraquinones including chrysophanol, emodin, and rhein could reverse these aberrant changes. They could significantly inhibit pro-fibrotic protein expressions including collagen I, α-SMA, fibronectin, and vimentin in the kidney tissues of the adenine-induced CRF rats. Of note, SKI and rhein showed the stronger inhibitory effect on these pro-fibrotic protein expressions than chrysophanol and emodin. Furthermore, they could improve dysregulation of IƙB/NF-ƙB and Keap1/Nrf2 signaling pathways. Chrysophanol and emodin showed the stronger inhibitory effect on the NF-κB p65 protein expression than SKI and rhein. Rhein showed the strongest inhibitory effect on p65 downstream target gene products including NAD(P)H oxidase subunits (p47phox, p67phox, and gp91phox) and COX-2, MCP-1, iNOS, and 12-LO in the kidney tissues. However, SKI and rhein showed the stronger inhibitory effect on the significantly downregulated anti-inflammatory and anti-oxidative protein expression nuclear Nrf2 and its target gene products including HO-1, catalase, GCLC, and NQO1 in the Keap1/Nrf2 signaling pathway than chrysophanol and emodin. This study first demonstrated that SKI and its major components protected against renal fibrosis by inhibiting oxidative stress and inflammation via simultaneous targeting IƙB/NF-ƙB and Keap1/Nrf2 signaling pathways, which illuminated the potential molecular mechanism of anti-oxidative and anti-inflammatory effects of SKI.

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“…Intriguingly, natural products are one of the most promising therapies for a broad spectrum of refractory diseases including coronavirus disease 2019 and its complications ( Chen et al, 2018a ; Chen et al, 2018b ; Izzo et al, 2020 ; Yang et al, 2021a ; Yang et al, 2021b ; Zhang et al, 2021b ; Singla et al, 2021 ; Zuo et al, 2021 ). Mounting natural products have been demonstrated to exhibit excellent efficacy for CKD treatment ( Wang et al, 2018b ; Zhang et al, 2020c ; Geng et al, 2020 ; Meng et al, 2020 ; Miao et al, 2020 ; Lan, 2021 ; Li et al, 2021 ; Luo et al, 2021 ; Miao et al, 2022 ; Yu et al, 2022 ). Although a number of natural products could mitigate MN, the natural products in MN application are still in its infancy compared with CKD.…”

Section: Treatment Of Membranous Nephropathymentioning

confidence: 99%

Recent Advances in Clinical Diagnosis and Pharmacotherapy Options of Membranous Nephropathy

et al. 2022

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Membranous nephropathy (MN) is the most common cause of nephrotic syndrome among adults, which is the leading glomerular disease that recurs after kidney transplantation. Treatment for MN remained controversial and challenging, partly owing to absence of sensitive and specific biomarkers and effective therapy for prediction and diagnosis of disease activity. MN starts with the formation and deposition of circulating immune complexes on the outer area in the glomerular basement membrane, leading to complement activation. The identification of autoantibodies against the phospholipase A2 receptor (PLA2R) and thrombospondin type-1 domain-containing protein 7A (THSD7A) antigens illuminated a distinct pathophysiological rationale for MN treatments. Nowadays, detection of serum anti-PLA2R antibodies and deposited glomerular PLA2R antigen can be routinely applied to MN. Anti-PLA2R antibodies exhibited much high specificity and sensitivity. Measurement of PLA2R in immune complex deposition allows for the diagnosis of PLA2R-associated MN in patients with renal biopsies. In the review, we critically summarized newer diagnosis biomarkers including PLA2R and THSD7A tests and novel promising therapies by using traditional Chinese medicines such as Astragalus membranaceus, Tripterygium wilfordii, and Astragaloside IV for the treatment of MN patients. We also described unresolved questions and future challenges to reveal the diagnosis and treatments of MN. These unprecedented breakthroughs were quickly translated to clinical diagnosis and management. Considerable advances of detection methods played a critical role in diagnosis and monitoring of treatment.

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1‐Hydroxypyrene mediates renal fibrosis through aryl hydrocarbon receptor signalling pathway

Cited by 37 publications

References 71 publications

Estimated Renal Metabolomics at Reperfusion Predicts One-Year Kidney Graft Function

Estimated Renal Metabolomics at Reperfusion Predicts One-Year Kidney Graft Function

Shenkang Injection and Its Three Anthraquinones Ameliorates Renal Fibrosis by Simultaneous Targeting IƙB/NF-ƙB and Keap1/Nrf2 Signaling Pathways

Recent Advances in Clinical Diagnosis and Pharmacotherapy Options of Membranous Nephropathy

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