Abstract
Abstract Acute inflammation is accompanied by complement system activation and inflammatory cell accumulation. Acute kidney injury (AKI) is one of the common clinical symptoms, it is not clear whether complement system-mediated signaling pathway is involved. This study demonstrated that the expressions of complement C5a and C5a receptor (C5aR) protein in a mouse model with glycerol induced AKI were significantly increased, and the expression of inflammatory cytokines, such as IL-1β, IL-6 and TNF-α, were significantly higher than those in the blank control group. While C5aR antagonist (C5aRa) was added, western analyses for C5a and C5aR were reduced, meanwhile, qPCR and ELISA data showed that inflammatory cytokines also decreased significantly. In addition, preliminarily explored, the Mitogen-activated protein kinases (MAPKs) can be activated by the C5a/C5aR pathway in an AKI mouse model which showed that the C5a/C5aR pathway in a mouse model group activated ERK1/2 and p38, and the protein expression decreased when C5aRa was added. In conclusion, these results indicate that the C5a/C5aR pathway promotes renal pathogenesis by activating ERK1/2 and p38 expression and then affects the disease process, which has certain guiding significance for the subsequent clinical trial.
Highlights
Acute kidney injury (AKI) is a clinical syndrome caused by rapid decline of renal function in a short time brought along by various causes [1, 2]
In order to study the relation of C5a/C5a receptor (C5aR) pathway and ERK1/2 and p38MAPK in acute kidney injury, a prospective cohort study was conducted in an animal model
We set up four groups, such as blank control group, a model group, a C5aR antagonist (C5aRa)+ model group, and a C5aRa group to detect the expression of C5a and C5aR
Summary
AKI is a clinical syndrome caused by rapid decline of renal function in a short time brought along by various causes [1, 2]. The extremely high rates of mortality could be the development of distant organ injury [9] It should not be considered as a single disease [10], when AKI appears, the primary task is to determine the etiology as soon as possible. Apart from the inflammation response, C5a has been reported to modulate a tumor growth and metastasis [14, 15], which can increase the activation of extracellular signal-regulated kinase, such as p38 and Akt, promoting the formation of tumor [16,17,18]. Previous studies have demonstrated that there are several important signaling pathways which are involved in AKI-related cell death, such as MAPK-ERK pathway [22].
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