Abstract
ObjectiveThis study was designed to investigate the role of AQP1 in the development of LPS-induced AKI and its potential regulatory mechanisms in the inflammatory responses of macrophages.MethodsMale Wistar rats were injected intraperitoneally with LPS, and biochemical and histological renal damage was assessed. The levels of inflammatory mediators, macrophage markers and AQP1 in blood and kidney tissues were assessed by ELISA. RTPCR was used to assess changes in the relative levels of AQP1 mRNA induced by LPS. Western blot and immunofluorescence analyses were performed to assay the activation of the p38 MAPK and NF-κB pathways, respectively. The same detection methods were used in vitro to determine the regulatory mechanisms underlying AQP1 function.ResultsAQP1 mRNA levels were dramatically decreased in AKI rats following the increased expression of inflammatory factors. In vitro experiments demonstrated that silencing the AQP1 gene increased inflammatory mediator secretion, altered the classical activation of macrophages, greatly enhanced the phosphorylation of p38 and accelerated the translocation of NF-κB. Furthermore, these results were blocked by doramapimod, a p38 inhibitor. Therefore, these effects were mediated by the increased phosphorylation of p38 MAPK.ConclusionOur results suggest that altered AQP1 expression may be associated with the development of inflammation in AKI. AQP1 plays a protective role in modulating acute renal injury and can attenuate macrophage-mediated inflammatory responses by downregulating p38 MAPK activity in LPS-induced RAW264.7 cells. The pharmacological targeting of AQP1-mediated p38 MAPK signalling may provide a novel treatment approach for AKI.
Highlights
Inflammation is a complex biological response to injury caused by noxious physical or chemical factors and plays an important role in pathogen removal and tissue repair after injury [1]
We investigated whether AQP1 attenuates inflammatory responses via the p38 Mitogen-activated protein kinases (MAPKs) and NF-κB/ IκBα signalling pathways in RAW264.7 macrophages to determine whether AQP1 is a potential therapeutic target for Acute kidney injury (AKI)
Macrophages are known to contribute to inflammation and fibrosis in many kidney diseases [14, 15]
Summary
Inflammation is a complex biological response to injury caused by noxious physical or chemical factors and plays an important role in pathogen removal and tissue repair after injury [1]. Acute kidney injury (AKI) is an abnormal inflammatory response in critically ill patients that is induced by bacterial, viral or fungal infection and is associated with. Macrophages, a type of immune cell involved in the initiation, development, and resolution of inflammation, play significant roles in the development of renal injury. Anti-inflammatory M2 macrophages play an important role in tissue repair [5]. The Acute Dialysis Quality Initiative (ADQI) XIII Work Group proposed that macrophages are a therapeutic target involved in the process of tissue repair after AKI [8]
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