scholarly journals Long Non-coding RNA N1LR Protects Against Myocardial Ischemic/Reperfusion Injury Through Regulating the TGF-β Signaling Pathway

2021 ◽  
Vol 8 ◽  
Author(s):  
Lin Du ◽  
Jie Chen ◽  
Yong Wu ◽  
Guangwei Xia ◽  
Mingxing Chen ◽  
...  
Keyword(s):  
Reperfusion Injury ◽  
Signaling Pathway ◽  
Protective Factor ◽  
Transforming Growth Factor ◽  
H9c2 Cell ◽  
Cerebral Stroke ◽  
Ischemic Reperfusion Injury ◽  
Ischemic Reperfusion

Long non-coding RNAs (lncRNAs) have been shown to play critical roles in various cell biological processes. However, the mechanism of lncRNAs in acute myocardial infarction (AMI) is not fully understood. Previous studies showed that lncRNA N1LR was down-regulated in ischemic cerebral stroke and its up-regulation was protective. The current study was designed to assess the protective effect of N1LR and further to explore potential mechanisms of N1LR in ischemic/reperfusion (I/R) injury after AMI. Male C57BL/6J mice and H9c2 cardiomyocytes were selected to construct in vivo and in vitro pathological models. In H9c2 cell line, N1LR expression was markedly decreased after H2O2 and CoCl2 treatments and N1LR overexpression alleviated apoptosis, inflammation reaction, and LDH release in cardiomyocytes treated with H2O2 and CoCl2. Mouse in vivo study showed that overexpression of N1LR enhanced cardiac function and suppressed inflammatory response and fibrosis. Mechanistically, we found that the expression of transforming growth factor (TGF)-β1 and smads were significantly decreased in the N1LR overexpression group exposed to H2O2. In a summary, our study indicated that N1LR can act as a protective factor against cardiac ischemic-reperfusion injury through regulating the TGF-β/Smads signaling pathway.

scholarly journals Klotho Reduces Necroptosis by Targeting Oxidative Stress Involved in Renal Ischemic-Reperfusion Injury

2018 ◽  
Vol 45 (6) ◽  
pp. 2268-2282 ◽  
Author(s):  
Yingying Qian ◽  
Xiangjiang Guo ◽  
Lin Che ◽  
Xuejing Guan ◽  
Bei Wu ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Reperfusion Injury ◽  
Tunel Staining ◽  
Protective Effects ◽  
Oxidative Stress Biomarkers ◽  
Ischemic Reperfusion Injury ◽  
Ischemic Reperfusion ◽  
Renal Ischemic Reperfusion Injury

Background/Aims: Klotho is a multifunctional protein expressed predominantly in kidney tubular epithelium. Here, we investigated the protective effects of Klotho on necroptosis in renal ischemic-reperfusion injury (IRI) and the role of oxidative stress in this process. Methods: Mice were subjected to bilateral renal pedicle clamping. Mouse renal tubular epithelial (TCMK-1) cells were exposed to hypoxia/reoxygenation (H/R) or H2O2. Kidney samples from acute kidney injury (AKI) patients and controls were examined by immunofluorescence. Klotho protein and N-acetyl-L-cysteine (NAC) were used to define their roles in mediating necroptosis. Necroptosis was assessed by TUNEL staining, immunoblotting, and real-time PCR. Oxidative stress was studied via ELISA, immunoblotting, colorimetric, and thiobarbituric acid reactive substances assays. Results: Renal IRI induced Klotho deficiency in the serum and kidney, but an increase in the urine. The levels of the necroptotic markers receptor-interacting protein kinase (RIP) 1, RIP3, IL-1β, and TUNEL-positive cells increased after IRI; all increases were ameliorated by Klotho. In TCMK-1 cells, Klotho and NAC attenuated the elevation in RIP1, RIP3, and LDH release induced by H/R or H2O2. Moreover, Klotho decreased the levels of oxidative stress biomarkers and elevated superoxide dismutase 2 expression in both in vivo and in vitro experiments. Studies in human samples further confirmed the Klotho deficiency and increased formation of RIP3 puncta in AKI kidneys. Conclusion: Klotho protects tubular epithelial cells from IRI and its anti-necroptotic role may be associated with oxidative stress inhibition.

Renal ischemic-reperfusion injury in L-selectin-deficient mice

1996 ◽  
Vol 271 (2) ◽  
pp. F408-F413 ◽  
Author(s):  
H. Rabb ◽  
G. Ramirez ◽  
S. R. Saba ◽  
D. Reynolds ◽  
J. Xu ◽  
...  
Keyword(s):  
Reperfusion Injury ◽  
Neutrophil Migration ◽  
High Power Field ◽  
Ischemic Reperfusion Injury ◽  
Ischemic Reperfusion ◽  
Tubular Necrosis ◽  
Deficient Mice

L-selectin on leukocyte surfaces mediates cell rolling on endothelium. L-selectin blockade with antibodies attenuated ischemic-reperfusion injury (IRI) in heart and skeletal muscle, but its role in renal IRI is unknown. We evaluated the role of L-selectin in renal IRI using L-selectin-deficient mice. Neutrophil migration to chemically inflamed peritoneum was reduced by 47% (P < 0.01) in L-selectin-deficient mice. Ischemia was induced by bilateral renal pedicle clamping for 30 min. Control and L-selectin groups had similar elevations of serum creatinine (1.8 +/- 0.3 vs. 1.7 +/- 0.2 mg/dl) and blood urea nitrogen (111 +/- 17 vs. 128 +/- 12 mg/dl) 24 h postischemia. Pathological assessment showed comparable degrees of tubular necrosis at 24 h. The postischemic increase in peritubular neutrophils per 10 high-power field was similar in control and L-selectin-deficient groups at 4 (28 +/- 10 vs. 22 +/- 5), 12 (245 +/- 80 vs. 236 +/- 78), and 24 h (130 +/- 12 vs. 156 +/- 18). These data argue against a significant role for L-selectin in renal IRI. Patho-physiological roles of L-selectin in vivo appear to be more complex than in vitro data would suggest.

scholarly journals Regorafenib-Attenuated, Bleomycin-Induced Pulmonary Fibrosis by Inhibiting the TGF-β1 Signaling Pathway

2021 ◽  
Vol 22 (4) ◽  
pp. 1985
Author(s):  
Xiaohe Li ◽  
Ling Ma ◽  
Kai Huang ◽  
Yuli Wei ◽  
Shida Long ◽  
...  
Keyword(s):  
Pulmonary Fibrosis ◽  
Signaling Pathway ◽  
Transforming Growth Factor ◽  
Kinase Inhibitor ◽  
In Vivo Experiments ◽  
Age Related ◽  
And Migration ◽  
Tgf Β1

Idiopathic pulmonary fibrosis (IPF) is a fatal and age-related pulmonary disease. Nintedanib is a receptor tyrosine kinase inhibitor, and one of the only two listed drugs against IPF. Regorafenib is a novel, orally active, multi-kinase inhibitor that has similar targets to nintedanib and is applied to treat colorectal cancer and gastrointestinal stromal tumors in patients. In this study, we first identified that regorafenib could alleviate bleomycin-induced pulmonary fibrosis in mice. The in vivo experiments indicated that regorafenib suppresses collagen accumulation and myofibroblast activation. Further in vitro mechanism studies showed that regorafenib inhibits the activation and migration of myofibroblasts and extracellular matrix production, mainly through suppressing the transforming growth factor (TGF)-β1/Smad and non-Smad signaling pathways. In vitro studies have also indicated that regorafenib could augment autophagy in myofibroblasts by suppressing TGF-β1/mTOR (mechanistic target of rapamycin) signaling, and could promote apoptosis in myofibroblasts. In conclusion, regorafenib attenuates bleomycin-induced pulmonary fibrosis by suppressing the TGF-β1 signaling pathway.

scholarly journals Inhibition of TGF-β Signaling in Gliomas by the Flavonoid Diosmetin Isolated from Dracocephalum peregrinum L.

Molecules ◽  
2020 ◽  
Vol 25 (1) ◽  
pp. 192 ◽  
Author(s):  
Yuli Yan ◽  
Xingyu Liu ◽  
Jie Gao ◽  
Yin Wu ◽  
Yuxin Li
Keyword(s):  
Signaling Pathway ◽  
Caspase 3 ◽  
Transforming Growth Factor ◽  
Glioma Cells ◽  
Chinese Herbs ◽  
Migration And Invasion ◽  
Western Blots ◽  
E Cadherin

Background: Dracocephalum peregrinum L., a traditional Kazakh medicine, has good expectorant, anti-cough, and to some degree, anti-asthmatic effects. Diosmetin (3′,5,7-trihydroxy-4′-methoxyflavone), a natural flavonoid found in traditional Chinese herbs, is the main flavonoid in D. peregrinum L. and has been used in various medicinal products because of its anticancer, antimicrobial, antioxidant, estrogenic, and anti-inflammatory effects. The present study aimed to investigate the effects of diosmetin on the proliferation, invasion, and migration of glioma cells, as well as the possible underlying mechanisms. Methods: 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), scratch wound, and Transwell assays were used to demonstrate the effects of diosmetin in glioma. Protein levels of Bcl-2, Bax, cleaved caspase-3, transforming growth factor-β (TGF-β), E-cadherin, and phosphorylated and unphosphorylated smad2 and smad3 were determined by Western blots. U251 glioma cell development and progression were measured in vivo in a mouse model. Results: Diosmetin inhibited U251 cell proliferation, migration, and invasion in vitro, the TGF-β signaling pathway, and Bcl-2 expression. In contrast, there was a significant increase in E-cadherin, Bax, and cleaved caspase-3 expression. Furthermore, it effectively reduced the tumorigenicity of glioma cells and promoted apoptosis in vivo. Conclusion: The results of this study suggest that diosmetin suppresses the growth of glioma cells in vitro and in vivo, possibly by activating E-cadherin expression and inhibiting the TGF-β signaling pathway.

scholarly journals Lipid Emulsion Improves Functional Recovery in an Animal Model of Stroke

2020 ◽  
Vol 21 (19) ◽  
pp. 7373
Author(s):  
Motomasa Tanioka ◽  
Wyun Kon Park ◽  
Joohyun Park ◽  
Jong Eun Lee ◽  
Bae Hwan Lee
Keyword(s):  
Reperfusion Injury ◽  
Signaling Pathway ◽  
Lipid Emulsion ◽  
Glycogen Synthase ◽  
Wnt Signaling Pathway ◽  
Sodium Pentobarbital ◽  
Ischemic Reperfusion Injury ◽  
Neuroprotective Effects ◽  
Ischemic Reperfusion ◽  
The Brain

Stroke is a life-threatening condition that leads to the death of many people around the world. Reperfusion injury after ischemic stroke is a recurrent problem associated with various surgical procedures that involve the removal of blockages in the brain arteries. Lipid emulsion was recently shown to attenuate ischemic reperfusion injury in the heart and to protect the brain from excitotoxicity. However, investigations on the protective mechanisms of lipid emulsion against ischemia in the brain are still lacking. This study aimed to determine the neuroprotective effects of lipid emulsion in an in vivo rat model of ischemic reperfusion injury through middle cerebral artery occlusion (MCAO). Under sodium pentobarbital anesthesia, rats were subjected to MCAO surgery and were administered with lipid emulsion through intra-arterial injection during reperfusion. The experimental animals were assessed for neurological deficit wherein the brains were extracted at 24 h after reperfusion for triphenyltetrazolium chloride staining, immunoblotting and qPCR. Neuroprotection was found to be dosage-dependent and the rats treated with 20% lipid emulsion had significantly decreased infarction volumes and lower Bederson scores. Phosphorylation of Akt and glycogen synthase kinase 3-β (GSK3-β) were increased in the 20% lipid-emulsion treated group. The Wnt-associated signals showed a marked increase with a concomitant decrease in signals of inflammatory markers in the group treated with 20% lipid emulsion. The protective effects of lipid emulsion and survival-related expression of genes such as Akt, GSK-3β, Wnt1 and β-catenin were reversed by the intra-peritoneal administration of XAV939 through the inhibition of the Wnt/β-catenin signaling pathway. These results suggest that lipid emulsion has neuroprotective effects against ischemic reperfusion injury in the brain through the modulation of the Wnt signaling pathway and may provide potential insights for the development of therapeutic targets.

In Vivo Cardioprotection by Pitavastatin From Ischemic-reperfusion Injury Through Suppression of IKK/NF-κB and Upregulation of pAkt–e-NOS

2011 ◽  
Vol 58 (2) ◽  
pp. 199-206 ◽  
Author(s):  
Salma Malik ◽  
Ashok Kumar Sharma ◽  
Saurabh Bharti ◽  
Saroj Nepal ◽  
Jagriti Bhatia ◽  
...  
Keyword(s):  
Reperfusion Injury ◽  
Ischemic Reperfusion Injury ◽  
Ischemic Reperfusion
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