2.5 ARDS
ARDS was known as non-cardiogenic respiratory failure with severely impaired pulmonary function, hypoxemia, and decreased pulmonary compliance, with around 30 million patients every year[101] and mortality rate ranging from 34.9% to 46.1% depending on the severity[102]. ARDS is caused by pulmonary infections (bacterial, viral, etc.), other significant infections (skin, genitourinary system, etc.), burns, particularly smoke inhalation, and all kinds of traumas[103]. There are no specialized treatment options, and therapy is still reliant on lung-protective mechanical ventilation.
When microorganisms, irritant mediators, and so on infiltrate the alveolar barrier, macrophages polarize from resident alveolar macrophages to the M1 phenotype at an early stage in response to Toll-like receptors (TLR) induced by infection, releasing pro-inflammatory factors such as IL-1, IL-6, and TNF-α, which are the first hurdle of lung immune response[104], while pro-inflammatory Inflammation is exacerbated by further activation and release of pro-inflammatory factors, chemokines, adhesion molecules, and so on. The main mechanism of ARDS is assumed to be the acute, widespread lung inflammation caused by this overwhelming immune response [105].
A large number of miRNAs, such as miR-146, miR-155, miR-221, and miR-222, have been noted to be stimulated upon TLR signaling activation, and lncRNAs such as Mirt2, THRIL, MALAT1, and lincRNA-21 are also altered upon TLR activation and negatively regulate TLR signaling as well as suppress pro-inflammatory factor expression[106]. MALAT1 is highly expressed in inflammation-activated macrophages, interacts with NF-κB, inhibits TLR signaling, and lowers TNF-α, IL-6 and other inflammatory factors [107]. HOTAIR affects the miR-30a-5p/PDE7A axis in LPS-induced ARDS, increases the release of inflammatory factors, and exacerbates the pulmonary inflammatory response[108].