Classic Signaling Pathways in Alveolar Injury and Repair Involved in Sepsis-Induced ALI/ARDS: New Research Progress and Prospect

Figure 2

Regulation of five signaling pathways on alveolar injury and repair during sepsis-induced ALI/ARDS. The activation of STAT3 can enhance the effect of proinflammatory macrophages (M1) on cytokine storm. The activation of STAT3 can also activate Treg cells to increase the secretion of IL-10 to promote the proliferation and differentiation of AT2 cells (lung regeneration) during the alveolar injury and repair. NF-κB pathway recruits M1 to produce cytokine (TNF-α, IL-6), which promote the cytokine storm and the development of ALI/ARDS. Inhibition of MAPK signaling pathway by dual-specificity phosphatase (DUSP) can inhibit inflammatory response in ALI/ARDS. The mTOR signaling pathway and Notch signaling pathway can promote M1 to produce cytokine to aggravate the inflammation of ALI/ARDS. FGF21 increases the incidence of ALI/ARDS by regulating glucose and lipid metabolism through the mTOR signaling pathway. MSC exosomes can inhibit ALI/ARDS by inducing autophagy and pulmonary regeneration. The Notch signaling pathway can also promote Dcreg cells to produce IL-10 to inhibit ALI/ARDS. DHMEQ: dehydroxymethylepoxyquinomicin; M1: proinflammatory macrophages; M2: anti-inflammatory macrophages; DUSP: dual-specificity phosphatase; BRL: BRL-44408 maleate; FGF21: fibroblast growth factor 21; Arg-1: Arginase-1; Treg cell: regulatory T cell; SIRT1: Sirtuins1; DCregs: regulatory dendritic cells.