Contribution of TFEB-mediated autophagy to tubulointerstitial fibrosis in mice with adenine-induced chronic kidney disease

Yuan, Huiqi; Zheng, Chaoyang; Zhu, Li; Song, Ziqing; Dai, Linfeng; Hu, Qingzong; Wang, Lei; Yang, Chen; Xiong, Jing

doi:10.1016/j.biopha.2020.110949

Cited by 14 publications

(20 citation statements)

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“…Moreover, trehalose induces TFEB expression and autophagy and reduces tubular injury and mitochondrial dysfunction induced by cisplatin both in mice and human proximal tubular cells [ 132 ]. However, trehalose promoted cell death and inflammation in rat kidney epithelial cells [ 133 ]. During murine IRI-AKI, TFEB is activated and upregulates genes of the CLEAR network, promoting autophagy.…”

Section: Novel Mitochondria-related Therapeutic Targets In Kidney Dis...mentioning

confidence: 99%

“…Regarding CKD, TFEB and its target genes were upregulated in mice with adenine-induced CKD and in patients with IgA nephropathy, but its role was not addressed in interventional studies [ 133 ]. However, TFEB was downregulated in human DKD, sub-totally nephrectomized rats, and other forms of kidney fibrosis; this could be mediated by TFEB deacetylation by HDAC6 [ 136 ].…”

Section: Novel Mitochondria-related Therapeutic Targets In Kidney Dis...mentioning

confidence: 99%

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Tubular Mitochondrial Dysfunction, Oxidative Stress, and Progression of Chronic Kidney Disease

et al. 2022

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Acute kidney injury (AKI) and chronic kidney disease (CKD) are interconnected conditions, and CKD is projected to become the fifth leading global cause of death by 2040. New therapeutic approaches are needed. Mitochondrial dysfunction and oxidative stress have emerged as drivers of kidney injury in acute and chronic settings, promoting the AKI-to-CKD transition. In this work, we review the role of mitochondrial dysfunction and oxidative stress in AKI and CKD progression and discuss novel therapeutic approaches. Specifically, evidence for mitochondrial dysfunction in diverse models of AKI (nephrotoxicity, cytokine storm, and ischemia-reperfusion injury) and CKD (diabetic kidney disease, glomerulopathies) is discussed; the clinical implications of novel information on the key role of mitochondria-related transcriptional regulators peroxisome proliferator-activated receptor gamma coactivator 1-alpha, transcription factor EB (PGC-1α, TFEB), and carnitine palmitoyl-transferase 1A (CPT1A) in kidney disease are addressed; the current status of the clinical development of therapeutic approaches targeting mitochondria are updated; and barriers to the clinical development of mitochondria-targeted interventions are discussed, including the lack of clinical diagnostic tests that allow us to categorize the baseline renal mitochondrial dysfunction/mitochondrial oxidative stress and to monitor its response to therapeutic intervention. Finally, key milestones for further research are proposed.

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Section: Novel Mitochondria-related Therapeutic Targets In Kidney Dis...mentioning

confidence: 99%

Section: Novel Mitochondria-related Therapeutic Targets In Kidney Dis...mentioning

confidence: 99%

Tubular Mitochondrial Dysfunction, Oxidative Stress, and Progression of Chronic Kidney Disease

et al. 2022

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“…Once renal fibrosis develops, most patients progress to irreversible end-stage renal disease, in which kidney transplantation with dialysis is the only therapeutic option [ 22 ]. Therefore, slowing down the progression of fibrosis could be an important strategy for preventing CKD [ 24 ].…”

Section: Introductionmentioning

confidence: 99%

“…In recent years, the relationship between autophagy and renal fibrosis has been reported in studies on renal inflammation and autophagy [ 22 , 24 , 34 ]. Autophagy is an important cellular mechanism for the intracellular lysosome-mediated degradation of damaged organelles, protein aggregates, and other macromolecules in the cytoplasm.…”

Section: Introductionmentioning

confidence: 99%

Anti-Fibrotic Effect of Synthetic Noncoding Decoy ODNs for TFEB in an Animal Model of Chronic Kidney Disease

Lee

Kim

Park

2022

IJMS

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Despite emerging evidence suggesting that autophagy occurs during renal interstitial fibrosis, the role of autophagy activation in fibrosis and the mechanism by which autophagy influences fibrosis remain controversial. Transcription factor EB (TFEB) is a master regulator of autophagy-related gene transcription, lysosomal biogenesis, and autophagosome formation. In this study, we examined the preventive effects of TFEB suppression on renal fibrosis. We injected synthesized TFEB decoy oligonucleotides (ODNs) into the tail veins of unilateral ureteral obstruction (UUO) mice to explore the regulation of autophagy in UUO-induced renal fibrosis. The expression of interleukin (IL)-1β, tumor necrosis factor-α (TNF-α), and collagen was decreased by TFEB decoy ODN. Additionally, TEFB ODN administration inhibited the expression of microtubule-associated protein light chain 3 (LC3), Beclin1, and hypoxia-inducible factor-1α (HIF-1α). We confirmed that TFEB decoy ODN inhibited fibrosis and autophagy in a UUO mouse model. The TFEB decoy ODNs also showed anti-inflammatory effects. Collectively, these results suggest that TFEB may be involved in the regulation of autophagy and fibrosis and that regulating TFEB activity may be a promising therapeutic strategy against kidney diseases.

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“…Atg5-mediated autophagy in proximal renal tubular epithelial cells (TECs) ameliorates renal fibrosis by reducing G2/M cell cycle arrest and inflammatory cell infiltration and cytokine production [ 9 ]. However, another study found that autophagy induced by the transcription factor EB can mediate the apoptosis of TECs, thereby aggravating the progression of renal fibrosis [ 10 ]. In a rat model of renal fibrosis following unilateral ureteral ligation (UUO), downregulation of autophagy alleviates disease progression [ 11 ].…”

Section: Introductionmentioning

confidence: 99%

Experimental Study on Danggui Shaoyao San Improving Renal Fibrosis by Promoting Autophagy

Fan

Chen

Liu

et al. 2022

Evidence-Based Complementary and Alternative Medicine

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Renal fibrosis could lead to chronic kidney disease (CKD) developing into the end-stage with its pathological manifestation is the deposition of extracellular matrix (ECM). Danggui Shaoyao San (DSS) is one of the widely used herbal formulas in ancient China, which has been proven to have efficacy in the treatment of CKD. The experiment employed TGF-β1 to stimulate the NRK-52E cells to establish a renal fibrosis model. With rapamycin (RAPA) used as the positive control, we detected the expression of fibronectin (FN), caspase-3, and autophagy-related proteins in the NRK-52E cells treated with DSS by Western blot and immunofluorescence assay. In order to further verify autophagy-promoting effects of DSS, we adopted 3-MA to inhibit autophagy. The experiment has found that DSS can lower the protein levels of FN and caspase-3 in the NRK-52E cells induced by TGF-β1. After TGF-β1 stimulation, the expression of LC3 II/I and Beclin 1 has decreased, and the protein levels of mTOR and p62 have increased. Consistent with rapamycin, DSS has significantly reduced these effects of TGF-β1. It has also been found that DSS can increase the expression of LC3 II/I and Beclin 1 proteins and can reduce the level of mTOR in cells treated with 3-MA, suggesting that DSS can promote autophagy. In conclusion, DSS has been proved to reduce the apoptosis and fibrosis of NRK-52E cells induced by TGF-β1, which may be achieved by promoting autophagy.

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Contribution of TFEB-mediated autophagy to tubulointerstitial fibrosis in mice with adenine-induced chronic kidney disease

Cited by 14 publications

References 40 publications

Tubular Mitochondrial Dysfunction, Oxidative Stress, and Progression of Chronic Kidney Disease

Tubular Mitochondrial Dysfunction, Oxidative Stress, and Progression of Chronic Kidney Disease

Anti-Fibrotic Effect of Synthetic Noncoding Decoy ODNs for TFEB in an Animal Model of Chronic Kidney Disease

Experimental Study on Danggui Shaoyao San Improving Renal Fibrosis by Promoting Autophagy

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