SPRED2 deficiency may lead to lung ischemia–reperfusion injury via ERK1/2 signaling pathway activation

Abstract

The activation of the ERK1/2 signaling pathway influences the severity of lung IRI, causing inflammation with neutrophil infiltration. SPRED2 may be a promising target for the suppression of lung IRI.

The role of neutrophil extracellular traps and TLR signaling in skeletal muscle ischemia reperfusion injury

“…The role of ERK signaling following IR injury is not yet completely elucidated, but most studies to date show decreased ERK signaling and/or decreased ERK1/2 phosphorylation in the injured tissue to be beneficial for tissue survival and regeneration [38][39][40][41][42][43] and ERK signaling has also been implicated in fibrotic diseases. 36,37,[65][66][67] In order to investigate the role of ERK signaling in IR injury, we analyzed the IR + ctx single-cell data set to characterize Erk1 and Erk2 gene expression in uninjured and injured skeletal muscle without treatment interventions.…”

“…37 Furthermore, inhibition of Mapk genes and decreased phosphorylation of ERK1/2 have protective effects in multiple organ systems by decreasing apoptosis and increasing cellular turnover. [38][39][40][41][42][43] In contrast, contradicting reports have shown increased activation of the same ERK pathways provide protection. [44][45][46] These differences suggest ERK signaling may vary depending on pathologic state/condition, thus the precise role in IR injury remains to be elucidated.…”

“…Studies have shown inhibition of ERK1/2 signaling has been shown to attenuate fibrosis by minimizing extracellular matrix deposition in several mouse models, including hepatic IR injury 36 and kidney fibrosis 37 . Furthermore, inhibition of Mapk genes and decreased phosphorylation of ERK1/2 have protective effects in multiple organ systems by decreasing apoptosis and increasing cellular turnover 38‐43 . In contrast, contradicting reports have shown increased activation of the same ERK pathways provide protection 44‐46 .…”

Spred2-deficiency enhances the proliferation of lung epithelial cells and alleviates pulmonary fibrosis induced by bleomycin

“…Spred2 is an endogenous inhibitor of the Ras/Raf/MEK/ ERK pathway involved in a variety of cellular processes, including cell proliferation and inflammation 26 . We previously examined the role of Spred2 in lung injuries by using two acute injury models; LPS-induced ALI and ischemia-reperfusion injury models 19,20 . In both studies, lung injury was exacerbated in the absence of Spred2 with increased inflammatory responses.…”

“…Particularly, Spred2 is expressed in various tissues, including the lung 16 – 18 . Our previous studies focusing on Spred2 demonstrated that Spred2 controls the development of lung inflammatory responses by negatively regulating the ERK pathway using an acute lung injury (ALI) model induced by lipopolysaccharide (LPS) 19 , 20 , leading us to the hypothesis that Spred2-deficiency may aggravates the development of PF.…”