H2S alleviates renal injury and fibrosis in response to unilateral ureteral obstruction by regulating macrophage infiltration via inhibition of NLRP3 signaling

Zhou, Yueyuan; Zhu, Xiaoyan; Wang, Xuan; Peng, Yi; Du, Jiankui; Yin, Hang; Yang, Hui; Ni, Xin; Zhang, Weiru

doi:10.1016/j.yexcr.2019.111779

Cited by 38 publications

(36 citation statements)

References 58 publications

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“…Conversely, NLRP3 is also involved in M2 polarization since NLRP3 transactivate IL-4 promoter to increase IL-4 expression (characteristic of M2 phenotype) in peripheral blood monocyte-derived Mϕ [97]. In addition, it has been found in UUO mice that NLRP3 inflammasome activates NF-κB and IL-4/STAT6 signaling pathways and promotes M1 and M2 macrophage infiltration and renal injury [98]. Hence, indicating that targeting NLRP3 inflammasome in diabetes could act on Mϕ in diabetic nephropathy.…”

Section: Macrophages Phenotype Under the Control Of Bioactive Moleculmentioning

confidence: 99%

Macrophage Phenotype and Fibrosis in Diabetic Nephropathy

Calle

Hotter

2020

IJMS

139

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Diabetic nephropathy (DN) is the leading cause of end-stage renal disease globally. The primary initiating mechanism in DN is hyperglycemia-induced vascular dysfunction, but its progression is due to different pathological mechanisms, including oxidative stress, inflammatory cells infiltration, inflammation and fibrosis. Macrophages (Mφ) accumulation in kidneys correlates strongly with serum creatinine, interstitial myofibroblast accumulation and interstitial fibrosis scores. However, whether or not Mφ polarization is involved in the progression of DN has not been adequately defined. The prevalence of the different phenotypes during the course of DN, the existence of hybrid phenotypes and the plasticity of these cells depending of the environment have led to inconclusive results. In the same sense the role of the different macrophage phenotype in fibrosis associated or not to DN warrants additional investigation into Mφ polarization and its role in fibrosis. Due to the association between fibrosis and the progressive decline of renal function in DN, and the role of the different phenotypes of Mφ in fibrosis, in this review we examine the role of macrophage phenotype control in DN and highlight the potential factors contributing to phenotype change and injury or repair in DN.

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Section: Macrophages Phenotype Under the Control Of Bioactive Moleculmentioning

confidence: 99%

Macrophage Phenotype and Fibrosis in Diabetic Nephropathy

Calle

Hotter

2020

IJMS

139

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“…This viewpoint may be supported by the findings from the same group that treatment with increasing concentrations of NaHS had no effect on renal tubular cell survival, causing doubt about whether PAG is only inhibiting H 2 S production in this case [ 57 ]. Additionally, many studies have confirmed that endogenous H 2 S is protective against renal ischemia-reperfusion injury [ 61 , 62 , 63 , 64 ], renal fibrosis [ 65 , 66 , 67 ], and diabetic nephropathy [ 68 , 69 ]. In response to ischemia, H 2 S levels are diminished along with renal dysfunction, and inhibition of CBS leads to accumulation of homocysteine and renal ischemia-reperfusion injury [ 70 , 71 ].…”

Section: Discussionmentioning

confidence: 99%

Polysulfide and Hydrogen Sulfide Ameliorate Cisplatin-Induced Nephrotoxicity and Renal Inflammation through Persulfidating STAT3 and IKKβ

Sun

Leng

et al. 2020

IJMS

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Cisplatin, a widely used chemotherapy for the treatment of various tumors, is clinically limited due to its extensive nephrotoxicity. Inflammatory response in tubular cells is a driving force for cisplatin-induced nephrotoxicity. The plant-derived agents are widely used to relieve cisplatin-induced renal dysfunction in preclinical studies. Polysulfide and hydrogen sulfide (H2S) are ubiquitously expressed in garlic, and both of them are documented as potential agents for preventing and treating inflammatory disorders. This study was designed to determine whether polysulfide and H2S could attenuate cisplatin nephrotoxicity through suppression of inflammatory factors. In renal proximal tubular cells, we found that sodium tetrasulfide (Na2S4), a polysulfide donor, and sodium hydrosulfide (NaHS) and GYY4137, two H2S donors, ameliorated cisplatin-caused renal toxicity through suppression of the massive production of inflammatory cytokines, including tumor necrosis factor α (TNF-α), interleukin-1β (IL-1β), interleukin-6 (IL-6), and cyclooxygenase-2 (COX-2). Mechanistically, the anti-inflammatory actions of Na2S4 and H2S may be mediated by persulfidation of signal transducer and activator of transcription 3 (STAT3) and inhibitor kappa B kinase β (IKKβ), followed by decreased phosphorylation of STAT3 and IKKβ. Moreover, the nuclear translocation of nuclear transcription factor kappa B (NF-κB), and phosphorylation and degradation of nuclear factor kappa B inhibitor protein alpha (IκBα) induced by cisplatin, were also mitigated by both polysulfide and H2S. In mice, after treatment with polysulfide and H2S donors, cisplatin-associated renal dysfunction was strikingly ameliorated, as evidenced by measurement of serum blood urea nitrogen (BUN) and creatinine levels, renal morphology, and the expression of renal inflammatory factors. Our present work suggests that polysulfide and H2S could afford protection against cisplatin nephrotoxicity, possibly via persulfidating STAT3 and IKKβ and inhibiting NF-κB-mediated inflammatory cascade. Our results might shed light on the potential benefits of garlic-derived polysulfide and H2S in chemotherapy-induced renal damage.

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“…High inflammatory response and interstitial macrophage infiltration are associated with the induction of UUO (Silverstein et al, 2003). Growing evidence indicates that UUO diminishes the production of H 2 S and the expressions of CSE, CBS, and 3-MPST proteins (Han et al, 2017;Chen Q. et al, 2018;Chen Y. et al, 2018;Zhou et al, 2020). The deletion of CSE gene intensifies UUO-induced kidney fibrosis by increasing the interstitial collagen deposition, microphages infiltration, proinflammatory cytokine TNF-α and neutrophil marker Ly6G, mitochondrial damage, oxidative stress, and apoptosis (Han et al, 2017).…”

Section: Unilateral Ureteral Occlusionmentioning

confidence: 99%

“…However, the administration of H 2 S donors could restore UUO-induced alterations of the renal functions (Jiang et al, 2014). For instance, NaHS reverses the UUO-induced changes by suppressing the corresponding pathways, namely, NLRP3 , TGF-β1 (Jung et al, 2013;Song et al, 2014), and ROS-AMPK signaling cascades (Zhou et al, 2020). Likewise, GYY4137 can significantly reduce renal fibrosis, inflammation, and apoptosis in UUO-induced male Lewis rats by reducing the levels of EMT markers and inhibiting TGF-β1/Smad and MAPK pathways (Lin et al, 2018).…”

Section: Unilateral Ureteral Occlusionmentioning

confidence: 99%

“…Meanwhile, CSE and CBS produce H 2 S by catalyzing homocysteine (Hcy) and Cys in the transsulfuration pathway (Chen et al, 2004;Chiku et al, 2009). Low production of H 2 S and downregulation of CBS, CSE, and 3-MPST expressions have been reported in common renal disorders (Aminzadeh and Vaziri, 2011;Han et al, 2017;Chen Q. et al, 2018;Chen Y. et al, 2018;Zhou et al, 2020). Although the mechanism in the reduction and underproduction of H 2 S in common renal diseases is not yet clear, the supplementation with H 2 S donors can effectively restore H 2 S levels and ameliorate the disease state associated with low production of H 2 S (Song et al, 2014;Weber et al, 2017;Khukhlina et al, 2018;Akbari et al, 2019).…”

Section: Introductionmentioning

confidence: 99%

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Roles of Hydrogen Sulfide Donors in Common Kidney Diseases

et al. 2020

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Hydrogen sulfide (H 2 S) plays a key role in the regulation of physiological processes in mammals. The decline in H 2 S level has been reported in numerous renal disorders. In animal models of renal disorders, treatment with H 2 S donors could restore H 2 S levels and improve renal functions. H 2 S donors suppress renal dysfunction by regulating autophagy, apoptosis, oxidative stress, and inflammation through multiple signaling pathways, such as TRL4/NLRP3, AMP-activated protein kinase/mammalian target of rapamycin, transforming growth factor-β1/Smad3, extracellular signal-regulated protein kinases 1/ 2, mitogen-activated protein kinase, and nuclear factor kappa B. In this review, we summarize recent developments in the effects of H 2 S donors on the treatment of common renal diseases, including acute/chronic kidney disease, renal fibrosis, unilateral ureteral obstruction, glomerulosclerosis, diabetic nephropathy, hyperhomocysteinemia, drug-induced nephrotoxicity, metal-induced nephrotoxicity, and urolithiasis. Novel H 2 S donors can be designed and applied in the treatment of common renal diseases.

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H2S alleviates renal injury and fibrosis in response to unilateral ureteral obstruction by regulating macrophage infiltration via inhibition of NLRP3 signaling

Cited by 38 publications

References 58 publications

Macrophage Phenotype and Fibrosis in Diabetic Nephropathy

Macrophage Phenotype and Fibrosis in Diabetic Nephropathy

Polysulfide and Hydrogen Sulfide Ameliorate Cisplatin-Induced Nephrotoxicity and Renal Inflammation through Persulfidating STAT3 and IKKβ

Roles of Hydrogen Sulfide Donors in Common Kidney Diseases

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