scholarly journals Tofacitinib Ameliorates Lipopolysaccharide-Induced Acute Kidney Injury by Blocking the JAK-STAT1/STAT3 Signaling Pathway

2021 ◽  
Vol 2021 ◽  
pp. 1-9
Author(s):  
Yang Yun ◽  
Jingyu Chen ◽  
Xuejiao Wang ◽  
Yingzhuo Li ◽  
Zhifan Hu ◽  
...  
Keyword(s):  
Acute Kidney Injury ◽  
Kidney Injury ◽  
Inhibitory Effect ◽  
Janus Kinase ◽  
Protective Effects ◽  
Lps Challenge ◽  
Stat3 Signaling ◽  
Stat3 Signaling Pathway ◽  
Septic Acute Kidney Injury ◽  
Underlying Mechanisms

Septic acute kidney injury (AKI) is the most common AKI syndrome in the intensive care unit (ICU), and it accounts for approximately half of AKI cases. Tofacitinib (TOFA) is a pan-Janus kinase (JAK) inhibitor that exhibits potent anti-inflammatory activity in rheumatoid arthritis. However, no study has examined the functional role of TOFA in septic AKI. In the present study, we investigated the protective effects of TOFA on septic AKI and the underlying mechanisms. A lipopolysaccharide- (LPS-) induced AKI model was established in C57BL/6 mice via an intraperitoneal injection of LPS (10 mg/kg). One hour after LPS challenge, the mice were orally administered TOFA (5, 10, or 15 mg/kg) every 6 h until sacrifice at 24 h. We found that TOFA significantly ameliorated LPS-induced renal histopathological changes and dysfunction. TOFA also suppressed the expression levels of proinflammatory cytokines (TNF-α, IL-1β, IL-6, and IFN-γ) and the parameters of oxidative stress (MDA, GSH, SOD, and CAT) in kidney tissues. These results may be associated with the inhibitory effect of TOFA on the JAK-STAT1/STAT3 pathway, which was significantly activated by LPS challenge. TOFA treatment also inhibited LPS-induced activation of the TLR4/NF-κB pathway. In conclusion, we revealed that TOFA had a protective effect on LPS-induced AKI, and it may be a promising therapeutic agent for septic AKI.

Inhibition of JAK2/STAT3 signaling pathway protects mice from the DDP-induced acute kidney injury in lung cancer

2019 ◽  
Vol 68 (9) ◽  
pp. 751-760 ◽  
Author(s):  
Lei Zhang ◽  
Peng Lu ◽  
Xu Guo ◽  
Ting Liu ◽  
Xu Luo ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Acute Kidney Injury ◽  
Signaling Pathway ◽  
Kidney Injury ◽  
Stat3 Signaling ◽  
Stat3 Signaling Pathway

scholarly journals Total Coumarins fromHydrangea paniculataProtect against Cisplatin-Induced Acute Kidney Damage in Mice by Suppressing Renal Inflammation and Apoptosis

2017 ◽  
Vol 2017 ◽  
pp. 1-15 ◽  
Author(s):  
Zhang Sen ◽  
Ma Jie ◽  
Yang Jingzhi ◽  
Wang Dongjie ◽  
Zhang Dongming ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Southern China ◽  
Kidney Injury ◽  
Kidney Damage ◽  
Renal Inflammation ◽  
Tubular Cells ◽  
Stat3 Signaling ◽  
Inflammatory Status ◽  
Stat3 Signaling Pathway ◽  
Underlying Mechanisms

Aim.Hydrangea paniculata (HP) Sieb. is a medical herb which is widely distributed in southern China, and current study is to evaluate renal protective effect of aqueous extract of HP by cisplatin-induced acute kidney injury (AKI) in animal model and its underlying mechanisms.Materials and Methods.HP extract was prepared and the major ingredients were coumarin glycosides. AKI mouse models were established by single i.p. injection of 20 mg/kg cisplatin, and HP was orally administrated for total five times. The renal biochemical functions, pathological staining, kidney oxidative stress, and inflammatory status were measured. Apoptosis of tubular cells and infiltration of macrophages and neutrophils were also tested.Results.HP administration could improve the renal function by decreasing concentration of blood urea nitrogen (BUN) and creatinine and attenuates renal oxidative stress and tubular pathological injury and apoptosis; further research demonstrated that HP could inhibit the overproduction of proinflammatory cytokines and regulate caspase and BCL-2 family proteins. HP also reduced renal infiltration of macrophages and neutrophils, and its effect might be by downregulating phosphorylation of ERK1/2 and stat3 signaling pathway.Conclusions.This present study suggests that HP could ameliorate cisplatin induced kidney damage by antioxidation and suppressing renal inflammation and tubular cell apoptosis.

scholarly journals Curcumin attenuates inflammation and cell apoptosis through regulating NF-κB and JAK2/STAT3 signaling pathway against acute kidney injury

Cell Cycle ◽  
2020 ◽  
Vol 19 (15) ◽  
pp. 1941-1951 ◽  
Author(s):  
Hongkun Zhu ◽  
Xinjun Wang ◽  
Xiaoxiao Wang ◽  
Bei Liu ◽  
Yizhen Yuan ◽  
...  
Keyword(s):  
Acute Kidney Injury ◽  
Signaling Pathway ◽  
Cell Apoptosis ◽  
Kidney Injury ◽  
Stat3 Signaling ◽  
Stat3 Signaling Pathway

scholarly journals Betulinic Acid Attenuates T-2-Toxin-Induced Testis Oxidative Damage Through Regulation of the JAK2/STAT3 Signaling Pathway in Mice

Biomolecules ◽  
2019 ◽  
Vol 9 (12) ◽  
pp. 787 ◽  
Author(s):  
Jing Wu ◽  
Chenglin Yang ◽  
Juan Liu ◽  
Jiaxin Chen ◽  
Chao Huang ◽  
...  
Keyword(s):  
Oxidative Damage ◽  
Signaling Pathway ◽  
Betulinic Acid ◽  
B Cell Lymphoma ◽  
Janus Kinase ◽  
Protective Effects ◽  
Pentacyclic Triterpene ◽  
Stat3 Signaling ◽  
Stat3 Signaling Pathway ◽  
Testicular Injury

T-2 toxin is one of the most toxic type A trichothecene mycotoxins in nature, and it exhibits reproductive toxicity. Betulinic acid (BA) is a natural pentacyclic triterpene compound found in species of Betula, and it has been reported to have antioxidant activity. The aim of the present study was to investigate the protective effect of BA on T-2-toxin-induced testicular injury in mice and explore its molecular mechanism. Sixty adult male mice were randomly divided into groups. The mice were pretreated orally with BA (0.25, 0.5, and 1.0 mg/kg) daily for 14 days, and the T-2 toxin (4 mg/kg body weight) was administered via intraperitoneal injection to induce oxidative stress after the last administration of BA. BA pretreatment significantly increased the secreted levels of testosterone and sperm motility. Moreover, BA pretreatment significantly increased the total antioxidant capacity (T-AOC), the activity of SOD and CAT, and the content of GSH, and it reduced the content of MDA. Furthermore, BA relieved testicular injury and reduced the number of apoptotic cells, and it significantly decreased the protein expression of Janus kinase 2 (JAK2), signal transducers and activators of transcription 3 (STAT3), caspsae-3, and Bcl-2-associated X protein (Bax). BA also increased the expression of B-cell lymphoma-2 (Bcl-2). We suggest that BA reduced the oxidative damage induced by T-2 toxin, and that these protective effects may be partially mediated by the JAK2/STAT3 signaling pathway.

The Protective Effects of Protease Inhibitor MG-132 on Sepsis-Induced Acute Kidney Injury and Its Mechanisms

2021 ◽  
Vol 11 (2) ◽  
pp. 265-270
Author(s):  
Xiaobo Zhang ◽  
Ying Zhu ◽  
Ying Zhou ◽  
Bingru Fei
Keyword(s):  
Acute Kidney Injury ◽  
Western Blot ◽  
Cecal Ligation ◽  
Kidney Injury ◽  
Protective Effects ◽  
Serum Cystatin C ◽  
Hematoxylin And Eosin ◽  
Underlying Mechanisms ◽  
Control Sham

MG-132 is an aldehyde peptide proteasome inhibitor, which reduces the inflammatory response and exerts a protective effect on severe acute pancreatitis and associated lung injury of rats. However, the involvement of MG-132 in sepsis-induced acute kidney injury (AKI) and the underlying mechanisms remain unknow. In this study, SD rats were employed to induce sepsis by cecal ligation and puncture (CLP) method and then divided into control, sham, CLP, and CLP + MG-132. Histopathology observation was detected by hematoxylin and eosin staining. The levels of biomarkers representing renal function such as serum creatinine (Scr), blood urea nitrogen (BUN), serum cystatin C (Scys C), and indicators of AKI such as Kim-1, IL-18, α glutathione S-traferase (α-GST) and albumin were measured by ELISA. Western blot and immunohistochemistry were performed to measure Testican-1. In order to assess the role of Testican-1, the expression of β-catenin, c-myc and cyclinD1 were evaluated by western blot. The results indicated that the levels of SCr, BUN, Scys C, KIM-1, IL-18, GST-α and albumin were decreased after MG-132 treatment compared with CLP group. And both pathological injury and W/D ratio were obviously improved in the CLP + MG- 132 group. Furthermore, the level of Testican-1 increased in the CLP group while a decreased presented in the CLP + MG-132 group. The expression of β-catenin, c-myc and cyclinD1 were downregulated in the CLP + MG-132 group compared to the CLP group. Our findings suggested that MG-132 can protect against AKI via inhibiting Testican-1 through the Wnt/β-catenin pathway MG-132 served as a novel biomarker and therapeutic regimen for sepsis-induced AKI.

Protective Effect of Amygdalin on Acute Kidney Injury Caused by Sepsis

2021 ◽  
Vol 19 (4) ◽  
pp. 458-463
Author(s):  
Jing Yue ◽  
Hong Zhou ◽  
Zhenzhen Jiang
Keyword(s):  
Acute Kidney Injury ◽  
Signaling Pathway ◽  
Cell Apoptosis ◽  
Cecal Ligation ◽  
Kidney Injury ◽  
Janus Kinase ◽  
Cecal Ligation And Puncture ◽  
Signal Transducer ◽  
Septic Acute Kidney Injury ◽  
Transcription 3

Sepsis is a systemic response to infections that may culminate into a life-threatening syndrome, the most common cause of acute kidney injury. Despite increasing mortality associated with septic acute kidney injury, its pathogenesis is poorly understood resulting in limited treatment options. Amygdalin participates in the regulation of various signaling pathways including Janus kinase/signal transducer and activator of transcription 3 signaling pathway. This pathway is critical for initiating immune responses and controlling persistent inflammation in various conditions such as infection. Cecal ligation and puncture is a most frequently used method for modeling sepsis. In the rat cecal ligation and puncture model, the levels of serum creatinine and blood urea nitrogen, as well as the serum levels of proinflammatory cytokines (tumor necrosis factor-α, interleukin-6, and interleukin-18) are significantly elevated. Furthermore, cecal ligation and puncture promotes cell apoptosis with increased BCL2-associated X protein and reduced B-cell lymphoma 2 protein expression. In this study, we have observed amygdalin to reduce serum cytokine secretion and prevent renal cell apoptosis in kidney injury, thus ameliorate kidney injury. The protective role of amygdalin in septic acute kidney injury was mediated through inhibition of Janus kinase/signal transducer and activator of the transcription 3 signaling pathway.

TSC1 deletion in fibroblasts alleviates lipopolysaccharide-induced acute kidney injury

2018 ◽  
Vol 132 (19) ◽  
pp. 2087-2101 ◽  
Author(s):  
Junhui Shen ◽  
Zhong-Kai Cui ◽  
Fang Yao ◽  
Kai Li ◽  
Yue Zhang ◽  
...  
Keyword(s):  
Acute Kidney Injury ◽  
Renal Function ◽  
Kidney Injury ◽  
Negative Regulator ◽  
Amino Terminal ◽  
Lps Challenge ◽  
Septic Acute Kidney Injury ◽  
Mtorc1 Signaling ◽  
The Difference ◽  
Mtorc1 Activation

Mechanistic target of rapamycin complex 1 (mTORC1) signaling is active in inflammation, but its involvement in septic acute kidney injury (AKI) has not been shown. mTORC1 activation (p-S6) in renal fibroblasts was increased in a mouse AKI model induced by 1.5 mg/kg lipopolysaccharide (LPS). Deletion of tuberous sclerosis complex 1 (TSC1), an mTORC1 negative regulator, in fibroblasts (Fibro-TSC1−/−) inhibited the elevation of serum creatinine and blood urea nitrogen in AKI compared with that in TSC1fl/fl control mice. Endothelin-1 (EDN1) and phospho-Jun-amino-terminal kinase (p-JNK) were up-regulated in Fibro-TSC1−/− renal fibroblasts after LPS challenge. Rapamycin, an mTORC1 inhibitor, and bosentan, an EDN1 antagonist, eliminated the difference in renal function between TSC1fl/fl and Fibro-TSC1−/− mice after LPS injection. Rapamycin restored LPS-induced up-regulation of EDN1, endothelin converting enzyme-1 (ECE1), and p-JNK in TSC1-knockdown mouse embryonic fibroblasts (MEFs). SP600125, a Jun-amino-terminal kinase (JNK) inhibitor, attenuated LPS-induced enhancement of EDN1 and ECE1 in TSC1-knockdown MEFs without a change in phospho-S6 ribosomal protein (p-S6) level. The results indicate that mTORC1–JNK-dependent up-regulation of ECE1 elevated EDN1 in TSC1-knockout renal fibroblasts and contributed to improvement of renal function in Fibro-TSC1−/− mice with LPS-induced AKI. Renal fibroblast mTORC1 plays an important role in septic AKI.

Lif Deficiency Leads to Iron Transportation Dysfunction in Ameloblasts

2021 ◽  
pp. 002203452110119
Author(s):  
L. Fan ◽  
Y.J. Ou ◽  
Y.X. Zhu ◽  
Y.D. Liang ◽  
Y. Zhou ◽  
...  
Keyword(s):  
Tooth Development ◽  
Iron Status ◽  
Acid Resistance ◽  
Blue Staining ◽  
Maturation Stage ◽  
Wild Type ◽  
Stat3 Signaling ◽  
Stat3 Signaling Pathway ◽  
Stem Cell Pluripotency ◽  
Underlying Mechanisms

Leukemia inhibitory factor (LIF), a member of the interleukin 6 family of cytokines, is involved in skeletal metabolism, blastocyst implantation, and stem cell pluripotency maintenance. However, the role of LIF in tooth development needs to be elucidated. The aim of the present study was to investigate the effect of Lif deficiency on tooth development and to elucidate the functions of Lif during tooth development and the underlying mechanisms. First, it was found that the incisors of Lif-knockout mice had a much whiter color than those of wild-type mice. Although there were no structural abnormalities or defective mineralization according to scanning electronic microscopy and computed tomography analysis, 3-dimensional images showed that the length of incisors was shorter in Lif−/− mice. Microhardness and acid resistance assays showed that the hardness and acid resistance of the enamel surface of Lif−/− mice were decreased compared to those of wild-type mice. In Lif−/− mice, whose general iron status was comparable to that of the control mice, the iron content of the incisors was significantly reduced, as confirmed by energy-dispersive X-ray spectroscopy (EDS) and Prussian blue staining. Histological staining showed that the cell length of maturation-stage ameloblasts was shorter in Lif−/− mice. Likewise, decreased expression of Tfrc and Slc40a1, both of which are crucial proteins for iron transportation, was observed in Lif−/− mice and Lif-knockdown ameloblast lineage cell lines, according to quantitative reverse transcription polymerase chain reaction, immunohistochemistry, and Western blot. Moreover, the upregulation of Tfrc and Slc40a1 induced by Lif stimulation was blocked by Stattic, a signal transducer and activator of transcription 3 (Stat3) signaling inhibitor. These results suggest that Lif deficiency inhibits iron transportation in the maturation-stage ameloblasts, and Lif modulates expression of Tfrc and Slc40a1 through the Stat3 signaling pathway during enamel development.

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