PPARγ in Ischemia-Reperfusion Injury: Overview of the Biology and Therapy

Huang, Ruizhen; Zhang, Chiyu; Wang, Xing; Hu, Honglin

doi:10.3389/fphar.2021.600618

Cited by 14 publications

(14 citation statements)

References 166 publications

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“…Therefore, it is considered to be a promising therapeutic target for treating I/R injury. 49,50 In this study, we observed enhanced PPAR-γ expression and inhibited phosphorylated NF-κB p65 expression in LPS-treated macrophage cells, suggesting that the PPAR-γ/NF-κB signaling pathway is involved in the antiinflammatory mechanism of PBzyme. These results illustrate that PBzyme has an excellent antioxidative function, antiinflammatory effect, and outstanding potential in the treatment of I/R injured skin flaps.…”

Section: Resultssupporting

confidence: 49%

Prussian Blue Nanozyme Promotes the Survival Rate of Skin Flaps by Maintaining a Normal Microenvironment

Hou

Gao

et al. 2022

ACS Nano

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Ischemia−reperfusion (I/R) injury leads to a low success rate of skin flap transplantation in reconstruction surgery, thus requiring development of new treatments. Necroptosis and apoptosis pathways, along with overexpression of reactive oxygen species and pro-inflammatory factors in skin flap transplantation, are deemed as potential therapeutic targets. This study provides a paradigm for nanozyme-mediated microenvironment maintenance to improve the survival rate of the transplanted skin flap. Prussian blue nanozyme (PBzyme) with multiple intrinsic biological activities was constructed and selected for this proof-of-concept study. The prepared PBzyme shows anti-inflammatory, antiapoptotic, antinecroptotic, and antioxidant activities in both in vitro and in vivo models of I/R injured skin flaps. The multiple inhibitory effects of PBzyme maintained a normal microenvironment and thus significantly promoted the survival rate of the I/R injured skin flap (from 37.21 ± 8.205% to 79.61 ± 7.5%). Of note, PBzyme regulated the expression of the characteristic signal molecules of necroptosis, including Rip 1, Rip 3, and pMLKL, indicating that PBzyme may be a therapeutic agent for necroptosis-related diseases. This study shows great prospects for clinical application of PBzyme in the treatment of skin flaps via local administration.

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Section: Resultssupporting

confidence: 49%

Prussian Blue Nanozyme Promotes the Survival Rate of Skin Flaps by Maintaining a Normal Microenvironment

Hou

Gao

et al. 2022

ACS Nano

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“…Once activated by its agonists, downstream transcription and expression effects are regulated [ 13 ]. The activation of PPAR γ leads to the amelioration of renal, hepatic, cerebral, myocardial, and other tissues of IRI [ 14 ]. This indicates that PPAR γ is a potential therapeutic mediator in IRI.…”

Section: Discussionmentioning

confidence: 99%

Protective Effects of PPARγ on Renal Ischemia-Reperfusion Injury by Regulating miR-21

Huang

Zou

Zhang

et al. 2022

Oxidative Medicine and Cellular Longevity

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Renal ischemia-reperfusion injury (RIRI) is a common pathological process that causes kidney injury. Previous studies have indicated that both peroxisome proliferator-activated receptor γ (PPARγ) and microRNA-21 (miR-21) exert protective effects against RIRI. However, their relationship is not well understood. In the present study, we investigated the role of the PPARγ/miR-21/programmed cell death 4 (PDCD4) axis in IRI, both in vivo and in vitro. In vitro cell hypoxia/reoxygenation (H/R) and in vivo RIRI models were established, and cell viability, cell apoptosis, and key molecule expression profiles were analyzed. Our results showed that both PPARγ and miR-21 had protective effects against RIRI to varying degrees, and there was an interaction between PPARγ and miR-21. PPARγ could promote the expression of miR-21 and partially protect against RIRI by reducing the level of the miR-21 target protein (PDCD4). Our findings underscore the potential utility of future clinical investigations of PPARγ activation and targeting of the underlying miR-21/PDCD4/caspase-3 pathway, which may participate in the pathogenesis of human IRI.

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“…Inflammation is a major player in the development of ischemic injury that is initiated by leukocytes infiltration and proinflammatory cytokines production following I/R. 2 In the current study, inflammation was measured both systemically and locally. I/R systemically increased serum CRP and locally increased renal TNF-α level.…”

Section: Discussionmentioning

confidence: 99%

“…2 The mechanisms of I/R-induced acute kidney injury involve hypoperfusion, inflammation, and reactive oxygen species (ROS) production. 2 Leukocytes are among major players that may fuel the inflammatory response. During early phase of reperfusion, there is a rapid increase in the levels of various pro-inflammatory cytokines.…”

Section: Introductionmentioning

confidence: 99%

Pomegranate extract ameliorates renal ischemia/reperfusion injury in rats via suppressing NF-κB pathway

et al. 2021

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Inflammation and oxidative stress are the major pathways involved in ischemia–reperfusion (I/R)-induced renal injury. This study was designed to evaluate the potential effect of pomegranate against I/R-induced renal injury. I/R injury was induced in nephrectomized rats by unilateral occlusion of the left renal pedicle for 45 min followed by 24 h of perfusion. Pomegranate succeeded to decrease serum levels of creatinine, potassium, and urea nitrogen, along with increasing creatinine clearance. Pomegranate also decreased I/R-induced changes in histopathological examination. Pomegranate attenuated the renal inflammatory response reflected by the suppression of nuclear factor κB p65 DNA binding activity, the upregulation of inhibitory protein kappa B-alpha mRNA expression, the downregulation of mRNA and protein expression of tumor necrosis factor α, in addition to the reduced myeloperoxidase activity and mRNA expression. Additionally, pomegranate attenuated oxidative stress likely through the modulation of lipid peroxidation and antioxidant levels reflected by the decreased MDA content and the increased glutathione level and superoxide dismutase activity. Results confirm the potential protective effect of pomegranate against I/R-induced renal injury through its anti-inflammatory and anti-oxidant effects mediated through the upregulation of inhibitory protein kappa B-alpha, the inhibition of NF-κB activity, and the associated TNF-α release, neutrophil infiltration, and oxidative stress.

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PPARγ in Ischemia-Reperfusion Injury: Overview of the Biology and Therapy

Cited by 14 publications

References 166 publications

Prussian Blue Nanozyme Promotes the Survival Rate of Skin Flaps by Maintaining a Normal Microenvironment

Prussian Blue Nanozyme Promotes the Survival Rate of Skin Flaps by Maintaining a Normal Microenvironment

Protective Effects of PPARγ on Renal Ischemia-Reperfusion Injury by Regulating miR-21

Pomegranate extract ameliorates renal ischemia/reperfusion injury in rats via suppressing NF-κB pathway

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