Abstract
Purpose To investigate the role and related mechanisms of miR-106a in sepsis-induced AKI.Methods Serum from sepsis and healthy patients was collected, sepsis mouse model was established by cecal ligation and puncture (CLP). TCMK-1 cells were treated with lipopolysaccharide (LPS) and transfected with THBS2-small interfering RNA (siTHBS2), miR-106a inhibitor, miR-106a mimics and their negative controls (NCs). The expression of miR-106a, thrombospondin 2 (THBS2), Bax, cleaved caspase-3 and Bcl-2, cell viability, relative caspase-3 activity and TNF-α, IL-1β, IL-6 content were respectively detected by quantitative real-time polymerase chain reaction (qRT-PCR), western blotting, Cell Counting Kit-8 (CCK-8) and enzyme linked immunosorbent assay (ELISA). The relationship between miR-106a and THBS2 was confirmed by dual luciferase reporter assay.Results MiR-106a was up-regulated in serum of sepsis patients, CLP-induced mice models and LPS-induced TCMK-1 cells. LPS reduced cell viability and Bcl-2 expression, and increased caspase-3 activity, Bax expression, the content of TNF-α, IL-1β, IL-6. THBS2 was a target of miR-106a. The decreases of caspase-3 activity, TNF-α, IL-1β, IL-6, Bax expression and the increases of cell viability, Bcl-2 expression caused by miR-106a knockdown were reversed when THBS2 silencing in LPS-stimulated TCMK-1 cells.Conclusion MiR-106a aggravated LPS-induced inflammation and apoptosis of TCMK-1 cells via regulating THBS2 expression.
Highlights
Sepsis is a systemic inflammatory response syndrome caused by infection or highly suspicious infection, and is a major cause of multiple organ failure and septic shock until death[1,2]
MiR-106a was up-regulated in serum of sepsis patients and cecal ligation and puncture (CLP)-induced mice models
Cell Counting Kit-8 (CCK-8) results in Figure 2B showed that cell viability was decreased in cells treated with only LPS, Figure 1 - MiR-106a was up-regulated in serum of sepsis patients and CLP-induced mice models
Summary
Sepsis is a systemic inflammatory response syndrome caused by infection or highly suspicious infection, and is a major cause of multiple organ failure and septic shock until death[1,2]. The uncontrolled inflammatory response and immune dysfunction of the body are the main pathophysiological basis of sepsis[2]. The degree of excessive inflammation and immune dysfunction directly affect the occurrence and development of sepsis[2]. Acute kidney injury (AKI) is one of the most common organ failure symptoms in sepsis[3]. The pathways of AKI induced by sepsis may include coagulopathy, inflammation, oxidative stress and changes in renal tubular epithelial cells to injury[4]. The mechanism of these effects is complex and there is no clear research report at present
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