Human umbilical cord mesenchymal stem cell exosomes alleviate sepsis-associated acute kidney injury via regulating microRNA-146b expression

MicroRNA‐146b correlates with decreased acute respiratory distress syndrome risk, reduced disease severity, and lower 28‐day mortality in sepsis patients

“…For instance, miR‐146b is down‐regulated in the myocardium tissue of sepsis mouse model, and overexpression of miR‐146b suppresses interleukin‐1β expression and myocardium apoptosis in sepsis mouse model by targeting the Notch1 pathway 15 . Meanwhile, the up‐regulation of miR‐146b reduced Scr and blood urea nitrogen levels; additionally, the up‐regulation of miR‐146b inhibits the NF‐κB pathway to suppress inflammation in sepsis‐induced acute kidney injury mouse model 14 . Moreover, overexpression of miR‐146b could reduce pro‐inflammatory cytokines and chemokines through modulating Toll‐like receptor 4 (TLR4), myeloid differentiation primary response (MyD88), TNF receptor‐associated factor 6 (TRAF6), and interleukin‐1 receptor‐associated kinase 1 (IRAK‐1) pathways in sepsis cell model 20 .…”

“…(d) miR-146b down-regulation might enhance inflammation and exacerbate injury of multiple organs (as was mentioned above12,14,20 ), thus increasing disease severity of sepsis patients; therefore, miR-146b was negatively correlated with APACHE II score and SOFA score in sepsis patients. Correlation of miR-146b with biochemical indexes, APACHE II score, and SOFA score in sepsis patients Correlation was determined by Spearman's rank correlation test.Abbreviations: APACHE II, Acute Physiology and Chronic Health Evaluation II; CRP, C-reactive protein; Scr, serum creatinine; SOFA, Sequential Organ Failure Assessment; WBC, white blood cell.…”

“…[10][11][12] According to previous studies, miR-146b could modulate the Notch1 pathway to suppress inflammation, thus ameliorating sepsis-induced multiple organ injury such as myocardial injury and acute kidney injury. [12][13][14] Meanwhile, it is suggested that miR-146b might regulate the nuclear factor-κB (NF-κB) pathway to inhibit the inflammatory response, thereby acting as a protective regulator in the progression of acute lung injury and pneumonia. 15,16 Additionally, miR-146b was reduced in sepsis patients compared with healthy individuals in our pilot study.…”

“…It is reported that miR‐146b is highly involved in regulating the inflammation, thus participating in the progression of various diseases including cancers, cardiovascular diseases, and notably, sepsis 10‐12 . According to previous studies, miR‐146b could modulate the Notch1 pathway to suppress inflammation, thus ameliorating sepsis‐induced multiple organ injury such as myocardial injury and acute kidney injury 12‐14 . Meanwhile, it is suggested that miR‐146b might regulate the nuclear factor‐κB (NF‐κB) pathway to inhibit the inflammatory response, thereby acting as a protective regulator in the progression of acute lung injury and pneumonia 15,16 .…”

“…Data showed that miR-146b was negatively correlated with Scr, WBC, CRP, APACHE II score, and SOFA score, while positively correlated with albumin in sepsis patients. Possible explanations might be that (a) reduced miR-146b might exacerbate apoptosis in renal tubular cells to enhance kidney injury in sepsis patients14 ; therefore, it was negatively correlated with Scr in sepsis patients; and (b) decreased miR-146b might activate several pro-inflammatory pathways such as the TRL4…”