1 Introduction

Acute lung injury (ALI) is a serious acute inflammation of the lungs caused by various direct or indirect factors such as diffuse lung parenchymal damage, increased permeability of alveolar walls and pulmonary capillaries, pulmonary interstitial and alveolar edema, and acute respiratory insufficiency. The pathophysiological characteristics of ALI are imbalance in ventilation/blood flow ratio and a significant decrease in lung compliance. The clinical manifestations of ALI include respiratory distress and progressive hypoxemia. When the oxygenation index of a patient with ALI is less than 300, it is called acute respiratory distress syndrome (ARDS). The etiology and mechanism of ALI are complex. Over the past half century, research regarding ALI/ARDS has made great progress, but the exact pathogenesis has not been fully clarified. A large number of studies have shown that the root cause of ALI is system inflammatory reaction syndrome (SIRS) caused by various injurious factors within and outside the lungs [1]. A variety of inflammatory cells are recruited and activated in the lungs under various direct and indirect harmful stimuli, and release a large number of pro-inflammatory mediators, causing the "cascade effect" of inflammatory cytokines, which leads to a runaway inflammatory response. In recent years, increasing number of experimental studies have found that the cause of ALI is the excessive immune response induced by infection rather than the pathogen itself [2]. Extensive and serious damage has occurred to lung epithelial cells and pulmonary vascular endothelial cells, which ultimately leads to pathological changes in ALI. It can be seen that the root cause of ALI is the "cascade effect" of inflammatory cytokines [3]. Therefore, the prevention and treatment strategy of ALI should mainly be considered from the inhibition of the overexpression of inflammatory mediators. Regulating the occurrence and development of inflammatory reactions has important clinical significance in preventing the occurrence of ALI and reducing mortality.

microRNAs (miRNAs) are small-sized RNA molecules and are involve in the regulation of gene expression mainly via binding with the 3′UTR region of the target transcripts [4]. miRNAs can maintain the physiological homeostasis of the body, and affect the development of diseases. miRNAs have been widely studied and recognized in many kinds of diseases, such as infectious diseases, tumors, cardiovascular diseases and genetic diseases. In recent years, miRNAs have become a research hotspot in the field of gene regulation at home and abroad. miRNAs bind to the 3′-UTR region of the target gene in the form of base complementation, which can inhibit the degradation or translation of the target gene. The number of miRNAs is small, accounting for only 1–3% of the total number of human genes, but it can regulate the expression of more than 30% of the total number of genes. It has been found that miRNAs are also closely related to the occurrence and development of lung diseases such as pneumonia, lung cancer and pulmonary fibrosis [5]. It has been demonstrated that miRNAs are involve in regulating the occurrence and development of immune response in sepsis-induced ALI, and are expected to become therapeutic targets and biomarkers in assisting diagnosis and judging the therapeutic effect of sepsis-induced ALI [6, 7].

2 Discussion

In 1998, Gattinoni et al. found that ALI caused by pneumonia or abdominal diseases had significant differences in pathological changes [8]. According to this phenomenon, ALI was divided into endogenous ALI and exogenous ALI. The main causes of endogenous ALI are pulmonary infection (bacteria, viruses, pneumocystis), drowning, toxic gas inhalation, and pulmonary trauma [9]. The main causes of exogenous ALI are sepsis caused by extrapulmonary factors, severe trauma, extracorporeal circulation, excessive infusion during resuscitation, and pancreatitis [9]. The pathological damage of endogenous ALI first affects the alveolar epithelium, and promotes the activation of alveolar macrophages and inflammatory response chain, leading to inflammatory response in the lung [10]. Exogenous ALI is caused by the activation of extrapulmonary inflammatory mediators and enters the lungs through the circulatory system to cause further damage. The early pathological changes of endogenous ALI were confined to the alveolar cavity, while pulmonary interstitial edema was more obvious in exogenous ALI. ALI caused by sepsis is the main type of exogenous ALI [11].

In sepsis, many miRNAs are involve in the occurrence and development of ALI. Ren H et al. found that down-regulation of miR-19a-3p could alleviate sepsis-induced ALI by enhancing the expression of USP13 [12]. Similarly, Jiang L found that methylation of the miR-19b-3p promoter exacerbates the inflammatory response in sepsis-induced ALI by targeting KLF7 [6]. miR-21 inhibits LPS-induced ALI by targeting nuclear factor-κB [13]. In a mouse model of LPS-induced ALI, miR-34b-5p knockdown alleviated lung inflammation and apoptosis by targeting PGRN [14]. miR-92a-3p regulates LPS-induced lung inflammation, oxidative stress and ALI in mice through AKAP1 [15]. miR-124 alleviates ALI in septic shock mice by downregulating MAPK14 and inhibiting the activation of MAPK signaling pathway [16]. miR-128-3p can alleviate sepsis-induced ALI by inhibiting the expression of PEL12 [17]. miR-129 inhibits pneumonia and apoptosis via regulating TAK1/NF-κB signaling pathway, thereby protecting mice from sepsis-induced ALI [18]. miR-129-5p prevents sepsis-induced ALI by reducing HMGB1 expression [19]. miR-139-5p improves sepsis-induced ALI by targeting Rho-kinase1 [20]. miR-144-3 aggravates LPS-induced ALI by down regulating Caveolin-2 and by activating JAK/STAT signaling pathway [21]. There are a lot of miRNAs involve in the occurrence and development of sepsis-induced ALI, as shown in Table 1. miRNAs secreted by different tissues can be released into the circulatory system and transported to the lungs, where they are internalized by recipient cells, mediating injury (Fig. 1). In addition to the above-mentioned role; as a therapeutic target for sepsis-induced ALI, miRNAs can also serve as potential diagnostic markers. Liu S et al. set up an animal model of ARDS by intraperitoneal injection of LPS in SD rats. After collected of serum and lung tissue, they found that serum miR-23a-5p was increased by sevenfold, fourfold and twofold at 3 h, 6 h, and 12 h after injection of LPS, which indicated that miR-23a-5p might be employed as potential biomarker for ARDS at the early stages [22]. Wang ZF et al. collected 156 samples of plasma from patients with sepsis, including 41 with ALI and 32 with ARDS, and found that the expression of miR-155 in plasma of patients with sepsis and ALI/ARDS were significantly higher than those of patients with sepsis but without ALI/ARDS [23]. miRNAs that have been studied and could be considered as diagnostic or prognostic markers are shown in Table 2.

Table 1 MicroRNAs involved in sepsis-induced ALI
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Fig. 1
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miRNAs from different cells participate in the pathophysiology of sepsis-induced ALI. miRNAs secreted by different cells can be released into the circulatory system and transported to lung, where they are internalized by recipient cells, mediating injury regulation. This figure was created with BioRender.com

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Table 2 MicroRNAs for the diagnosis of sepsis-induced ALI
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Since the discovery of miRNA in 1993, research on miRNA has attracted a lot of attention. The studies on these single stranded RNAs are helpful in improving people's understanding of cellular pathophysiology and molecular mechanisms. Several studies have shown that miRNAs play an important role in sepsis-induced ALI, including the regulation of inflammation, apoptosis, and oxidative stress, thereby participating in the progression of sepsis-induced ALI. Although there are still controversies surrounding the role of miRNAs in sepsis-induced ALI at present, many animal and human experimental results show that some miRNAs can act as therapeutic or diagnostic targets of sepsis-induced ALI. Also, the development of alternative or inhibitory drugs targeting specific miRNAs may be of great significance in treating sepsis-induced ALI and improving the prognosis of sepsis patients.