scholarly journals Mesenchymal Stem Cells Protect Against Sepsis-associated Acute Kidney Injury by Inducing Gal-9/Tim-3 to Remodel Immune Homeostasis

Author(s):  
congjuan luo ◽  
Feng Luo ◽  
Lin Che ◽  
Hui Zhang ◽  
Long Zhao ◽  
...  

Abstract Objective: The aim of the present study was to investigate the specific mechanism by which MSCs protect against SA-AKI.Methods: Male C57BL/6 mice underwent cecal ligation and puncture operation to induce sepsis and then received either normal IgG or MSCs (1* 106 cells intravenously) plus Gal-9 or soluble-Tim-3 3h after surgery. Results: After cecal ligation and puncture operation, injection with Gal-9 or MSCs plus Gal-9 had a higher survival rate than the IgG treatment group. Treatment with MSCs plus Gal-9 decreased serum creatinine and blood urea nitrogen levels and improved recovery of tubular function. Reduce the levels of IL-17, RORγt and induce the expression of IL-10 and FOXP3. Additionly, remodel the balance of TH17/Treg. However, when used soluble Tim-3 to block the Gal-9/Tim-3 pathway, the septic mice developed badly kidney injury and exhibited a higher mortality. Treatment with MSCs plus soluble Tim-3 blunted the therapeutic effect of MSCs, and inhibited the induction of Tregs and suppressed the inhibition of the differentiation to Th17 cells.Conclusion: Treatment with MSCs significantly reversed the TH1/TH2 balance. And the important mechanism for MSCs protection against SA-AKI maybe through the Gal-9/Tim-3 pathway.

2020 ◽  
Vol 19 (3) ◽  
pp. 270-276
Author(s):  
Jianying Wang ◽  
Xiaoting Yu

Acute kidney injury is a severe complication of sepsis. We have shown a protective effect of Platycodin D on sepsis induced acute kidney injury in an animal model that employs cecal ligation and puncture. Cecal ligation and puncture induced a series of degenerative changes in kidney, such as edema, hyperemia, and expansion in glomerular capillary, and inflammatory cells infiltration that were attenuated by Platycodin D. Also, rise in proinflammatory cytokine levels in septic rats was blunted by Platycodin D. Furthermore, Platycodin D administration reduced rise in serum levels of kidney injury markers-blood urea nitrogen and serum creatinine-in septic rats. Moreover, Platycodin D administration also suppressed the cell apoptosis in kidney that was associated with enhanced B-cell lymphoma 2 protein and reduced cleaved cysteine-aspartic protease-3 and BCL2-associated X protein. Lastly, Platycodin D administration attenuated sepsis-induced increase of phospho (p)-extracellular signal-regulated kinase, p-c-Jun NH2-terminal kinase, and p-p38. In conclusion, Platycodin D demonstrated protective effect against sepsis induced acute kidney injury through inactivation of mitogen activated protein kinase pathways, thus providing promising therapeutic strategy for the treatment of sepsis.


2018 ◽  
Vol 71 (4) ◽  
pp. 1921-1927 ◽  
Author(s):  
Carolina Ferreira Vasco ◽  
Mirian Watanabe ◽  
Cassiane Dezoti da Fonseca ◽  
Maria de Fátima Fernandes Vattimo

ABSTRACT Objective: To evaluate the antioxidant action of N-acetylcysteine and diosmin-hesperidin in an experimental model of sepsis-induced acute kidney injury in rats. Methods: The study used 20 Wistar adult male rats divided into the following groups: control (laparotomy with no induction of abdominal sepsis), sepsis (experimental model of sepsis with cecal ligation and puncture), N-acetylcysteine + sepsis and diosmin-hesperidin + sepsis. The evaluation contemplated physiological parameters (temperature, glycemia, and average blood pressure), kidney function (creatinine clearance), oxidative stress (urinary peroxides) and kidney histology. Results: The animals submitted to cecal ligation and puncture (sepsis) presented lower body temperature, lower average blood pressure, reduced creatinine clearance and increased urinary hydrogen peroxide levels. Treatment with diosmin-hesperidin improved kidney function and led to a reduction in the excretion of oxidative metabolites. Conclusion: The present study highlighted the protective antioxidant action of diosmin-hesperidin in the experimental model of sepsis-induced acute kidney injury.


2018 ◽  
Vol 8 (1) ◽  
Author(s):  
Satoshi Sunahara ◽  
Eizo Watanabe ◽  
Masahiko Hatano ◽  
Paul E. Swanson ◽  
Takehiko Oami ◽  
...  

2021 ◽  
Author(s):  
Navjot Pabla ◽  
Yogesh Scindia ◽  
Joseph Gigliotti ◽  
Amandeep Bajwa

Acute Kidney Injury (AKI) is a poor prognosis in hospitalized patients that is associated with high degree of mortality. AKI is also a major risk factor for development of chronic kidney disease. Despite these serious complications associated with AKI there has not been a great amount of progress made over the last half-century. Here we have outlined and provided details on variety of mouse models of AKI. Some of the mouse models of AKI are renal pedicle clamping (ischemia reperfusion injury), Cisplatin induced nephrotoxicity, sepsis (LPS, cecal slurry, and cecal ligation and puncture), folic acid, and rhabdomyolysis. In this chapter we describe in detail the protocols that are used in our laboratories.


2021 ◽  
Vol 19 (4) ◽  
pp. 458-463
Author(s):  
Jing Yue ◽  
Hong Zhou ◽  
Zhenzhen Jiang

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.


2017 ◽  
Vol 66 (4) ◽  
pp. 303-312 ◽  
Author(s):  
Guodong Sun ◽  
Wei Yang ◽  
Yang Zhang ◽  
Mingyan Zhao

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