miR-126 ameliorates multiple organ dysfunction in septic rats by regulating the differentiation of Th17/Treg

Abstract

Background The most common cause of death in sepsis is MODS. We hope that miR-126 can regulate the differentiation of Th17/Treg, reduce the infiltration of inflammatory factors in peripheral blood and various organs and tissues, and improve organ function and prognosis in sepsis. Methods and results Septic rat model was established by cecal perforation and ligation. miR-126 mimic and inhibitor were used to intervene sepsis. The experimental results showed that miR-126 mimic reduced the differentiation of Th17 and increased the differentiation of Treg in septic rats, resulting in the TNF-α, IL-6 and IL-17 were decreased in peripheral blood, the infiltration levels of TNF-α, IL-6 and IL-17 were decreased in lung, liver and kidney, the tissue damage degree of lung, liver and kidney were weakened, and the corresponding histopathological score decreased. Finally, the survival rate of septic rats was increased. However, after using miR-126 inhibitor, the levels of inflammatory factors and the degree of multiple organ injury in septic rats increased in varying degrees, and the prognosis of septic rats was worse. Conclusion This study confirmed that miR-126 can regulate the differentiation of Th17/Treg, change the infiltration of inflammatory factors in peripheral blood, lung, liver and kidney of septic rats, alleviate MODS, and improve the organ function and prognosis of septic rats.

LncRNA GAS5 relates to Th17 cells and serves as a potential biomarker for sepsis inflammation, organ dysfunctions and mortality risk

“…21 T cell differentiation into Th1 cell and Th17 cell plays an important role in the pathogenesis role in sepsis. 25,26 For instance, one study shows that Th17 cells induced immunosuppression plays a vital role in sepsis. 25 In our study, we found that lnc-GAS5 negatively correlated with Th17 cell and its secreted inflammatory cytokine (IL-17A), also However, this hypothesis needed further exploration.…”

“… 21 T cell differentiation into Th1 cell and Th17 cell plays an important role in the pathogenesis role in sepsis. 25 , 26 For instance, one study shows that Th17 cells induced immunosuppression plays a vital role in sepsis. 25 In our study, we found that lnc‐GAS5 negatively correlated with Th17 cell and its secreted inflammatory cytokine (IL‐17A), also it negatively associated with CRP which might be explained that (1) lnc‐GAS5 inhibited the T cell differentiation into Th17 cells, therefore it negatively associated with Th17 cells and IL‐17A in sepsis, and (2) lnc‐GAS5 restrained the inflammatory response, hence, it negatively correlated with CRP level in sepsis patients.…”

“…Another study exhibits that in monocytes, knockdown of lnc‐GAS5 might downregulate the macrophage M2 surface markers and concomitant increase in M1 markers, which implies that lnc‐GAS5 could promote the polarization of macrophage to M2 type but inhibit its polarization to M1 type 21 . T cell differentiation into Th1 cell and Th17 cell plays an important role in the pathogenesis role in sepsis 25,26 . For instance, one study shows that Th17 cells induced immunosuppression plays a vital role in sepsis 25 .…”

Improved Anticoagulant Effect of Layered Double Hydroxide‐Heparin Nanocomposites on the Microcirculation of Septic Rats

“…The pathological evaluation criteria were as follows: edema, structural changes, and inflammatory cell infiltration of various organ lesions, from light to heavy, were divided into four degrees corresponding to 0–4 points. (0, no or very slight damage; 1, mild injury; 2, moderate injury; 3, severe injury; and 4, very severe damage [ 65 ] ). The final score was the sum of the scores of each sample.…”

Circulating extracellular vesicles are associated with the clinical outcomes of sepsis

“…Recent studies suggest that EV caspase-1 activity can induce EC injury and that sepsis-induced pyroptosis of monocytes and ECs can release caspase-1 containing EVs ( 15 – 18 ). Conversely, EV miR-126 has been shown to stabilize the endothelium in sepsis while modulating sepsis-related organ failure ( 19 – 22 ). However, the potential role of circulating total or cell-specific EVs in septic patients and their association with sepsis outcomes such as organ failure and mortality are still largely unknown.…”