Urolithin A attenuates renal fibrosis by inhibiting TGF-β1/Smad and MAPK signaling pathways

Cheng, Zhengxing; Tu, Jingjing; Zhang, Hongpan; Zhang, Yi; Zhou, Benhong

doi:10.1016/j.jff.2021.104547

Cited by 10 publications

(13 citation statements)

References 54 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The pharmacological activities of UA against aging and several diseases have been reported in recent years, including the protect effective in the muscle, heart (Savi et al, 2017), brain (Tang et al, 2017), joints (Cui, Chen, & Shen, 2018), intestine (Larrosa et al, 2010), liver (Xia et al, 2020), and kidney (D'Amico et al, 2021). The impact of UA on renal diseases and its underlying mechanisms were revealed by a few studies (Cheng et al, 2021; Guada et al, 2017; Jing et al, 2019; Wang et al, 2019). In our previous studies, we showed that UA exerts protective effects against unilateral ureteral obstruction (UUO) induced renal fibrosis by inhibiting the TGF‐β1/SMAD and MAPK pathways (Cheng et al, 2021).…”

Section: Discussionmentioning

confidence: 99%

“…The impact of UA on renal diseases and its underlying mechanisms were revealed by a few studies (Cheng et al, 2021; Guada et al, 2017; Jing et al, 2019; Wang et al, 2019). In our previous studies, we showed that UA exerts protective effects against unilateral ureteral obstruction (UUO) induced renal fibrosis by inhibiting the TGF‐β1/SMAD and MAPK pathways (Cheng et al, 2021). In addition, UA could alleviate AKI induced by cisplatin by modulating inflammation and oxidative stress (Guada et al, 2017; Jing et al, 2019; Wang et al, 2019).…”

Section: Discussionmentioning

confidence: 99%

“…Briefly, after the mouse was anesthetized using isoflurane (induction concentration 1.5%, maintenance concentration 1%), its bilateral renal pedicles were clamped using specialized mouse arterial clamps for 25 min through nontraumatic clamps through an abdominal incision. Subsequently, the renal pedicles were orthotopically reconstituted for 24 h. The mice in UA treated groups received oral lavage and a different dose of UA for 7 days, once every day before being subjected to surgery, the timing and frequency as previously described (Cheng, Tu, Zhang, Zhang, & Zhou, 2021).…”

Section: Methodsmentioning

confidence: 99%

“…HK-2 cells were subjected to 24 h of hypoxia, followed by 12 h of reoxygenation treatment. In our previous study, we showed that UA at doses under 200 μM is not cytotoxic to HK-2 cells (Cheng et al, 2021). HK-2 cells were randomly divided into six groups: control, HR, HR + UA (20, 50, 100 μM), and HR + UA (100 μM) + ML385 (5 μM) groups (n = 3, means ± SEM).…”

Section: Ua Inhibits Ros Production In Hr-treated Hk-2 Cellsmentioning

confidence: 99%

See 3 more Smart Citations

Urolithin A alleviates acute kidney injury induced by renal ischemia reperfusion through the p62‐Keap1‐Nrf2 signaling pathway

Zhang

Liu

Zhang

et al. 2022

Phytotherapy Research

Self Cite

View full text Add to dashboard Cite

Acute kidney injury (AKI) induced by renal ischemia reperfusion (RIR) is typically observed in renal surgeries and is a leading cause of renal failure. However, there is still an unmet medical need currently in terms of clinical treatments. Herein, we report the effect of Urolithin A (UA) in a mouse RIR model, wherein we demonstrated its underlying mechanism both in vitro and in vivo. The expression levels of p62 and Keap1 significantly decreased, while that of nuclear Nrf2 increased in vitro in a hypoxia cell model after UA treatment. Furthermore, the apoptosis of tubular cells was attenuated and the reactive oxygen species (ROS) levels were reduced in the kidneys in a mouse RIR model after UA administration. In this study, we demonstrated that UA can alleviate oxidative stress and promote autophagy by activating the p62‐Keap1‐Nrf2 signaling pathway, which could protect the kidneys from ischemia reperfusion injury.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Ua Inhibits Ros Production In Hr-treated Hk-2 Cellsmentioning

confidence: 99%

See 2 more Smart Citations

Urolithin A alleviates acute kidney injury induced by renal ischemia reperfusion through the p62‐Keap1‐Nrf2 signaling pathway

Zhang

Liu

Zhang

et al. 2022

Phytotherapy Research

Self Cite

View full text Add to dashboard Cite

show abstract

“…A chronic fructose diet is a risk factor for hyperuricemic nephropathy. Urolithin A (UroA) is one of the major natural intestinal metabolites of ellagitannins found in pomegranates, berries, nuts, etc., with various pharmacological potentials ( Cheng et al, 2021 ; Zhang et al, 2022 ). However, the beneficial effect of UroA against hyperuricemic nephropathy and the underlying mechanism needs further investigation.…”

Section: Discussionmentioning

confidence: 99%

Urolithin A Attenuates Hyperuricemic Nephropathy in Fructose-Fed Mice by Impairing STING-NLRP3 Axis-Mediated Inflammatory Response via Restoration of Parkin-Dependent Mitophagy

et al. 2022

View full text Add to dashboard Cite

Urolithin A (UroA) is one of the primary intestinal metabolites of ellagitannins, showing translational potential as a nutritional intervention in humans. Mounting evidence suggests that fructose consumption contributes to the progression of chronic kidney disease (CKD) that manifests in hyperuricemic nephropathy, renal inflammation, and tubulointerstitial injury. Here, we investigated the efficacy of UroA in alleviating fructose-induced hyperuricemic nephropathy in mice. Uric acid-exposed human kidney-2 (HK-2) cells were utilized for in vitro mechanism validation. Histopathological staining, immunoblotting, and transmission electron microscope were performed for the mechanistic investigations. Our results revealed that UroA ameliorated fructose-induced hyperuricemic nephropathy in mice. The histopathologic assessment showed that UroA attenuated tubular hypertrophy and dilation, glomerular basement membrane thickening, and collagen deposition in the kidney of fructose-fed mice. Mechanistically, UroA treatment impaired STING-NLRP3 activation, resulting in reduced production of proinflammatory cytokines IL-1β, IL-6, and TNF-α. Notably, UroA exhibited a scavenging effect against reactive oxygen species (ROS) and restored fructose-impaired PINK1/Parkin-mediated mitophagy in nephropathic mice. Furthermore, the inhibitory effect of UroA in STING-NLRP3 activation was impaired after Parkin gene silencing in HK-2 cells. Together, this study suggests that UroA alleviates fructose-induced hyperuricemic nephropathy by promoting Parkin-dependent mitophagy, thereby suppressing STING-NLRP3 axis-mediated inflammatory response. Thus, dietary supplementation with UroA or ellagitannins-rich foods may serve as a promising intervention to prevent CKD progression.

show abstract

Natural coumarins: Preclinical evidence-based potential candidates to alleviate diabetic nephropathy

Ghosh

Rajanan

et al. 2022

Phytomedicine Plus

View full text Add to dashboard Cite

Urolithin A attenuates renal fibrosis by inhibiting TGF-β1/Smad and MAPK signaling pathways

Cited by 10 publications

References 54 publications

Urolithin A alleviates acute kidney injury induced by renal ischemia reperfusion through the p62‐Keap1‐Nrf2 signaling pathway

Urolithin A alleviates acute kidney injury induced by renal ischemia reperfusion through the p62‐Keap1‐Nrf2 signaling pathway

Urolithin A Attenuates Hyperuricemic Nephropathy in Fructose-Fed Mice by Impairing STING-NLRP3 Axis-Mediated Inflammatory Response via Restoration of Parkin-Dependent Mitophagy

Natural coumarins: Preclinical evidence-based potential candidates to alleviate diabetic nephropathy

Contact Info

Product

Resources

About