Growth Differentiation Factor 7 Prevents Sepsis-Induced Acute Lung Injury in Mice

Abstract

Objective. Acute lung injury (ALI) is a life-threatening complication during sepsis and contributes to multiple organ failure and high mortality for septic patients. The present study aims to investigate the role and molecular basis of growth differentiation factor 7 (GDF7) in sepsis-induced ALI. Methods. Mice were subcutaneously injected with recombinant mouse GDF7 Protein (rmGDF7) and then intratracheally injected with lipopolysaccharide (LPS) to generate sepsis-induced ALI. Primary peritoneal macrophages were isolated to further evaluate the role and underlying mechanism of GDF7 in vitro. Results. GDF7 was downregulated in LPS-stimulated lung tissues, and rmGDF7 treatment significantly inhibited inflammation and oxidative stress in ALI mice, thereby preventing LPS-induced pulmonary injury and dysfunction. Mechanistically, we found that rmGDF7 activated AMP-activated protein kinase (AMPK), and AMPK inhibition significantly blocked the anti-inflammatory and antioxidant effects of rmGDF7 during LPS-induced ALI. Further findings revealed that rmGDF7 activated AMPK through a downregulated stimulator of interferon gene (STING) in vivo and in vitro. Conclusion. GDF7 prevents LPS-induced inflammatory response, oxidative stress, and ALI by regulating the STING/AMPK pathway. Our findings for the first time identify GDF7 as a potential agent for the treatment of sepsis-induced ALI.

Research Progress of Macromolecules in the Prevention and Treatment of Sepsis

“…GDF7 can reduce inflammation and oxidative stress by downregulating stimulator of interferon genes, promoting adenosine 5′monophosphate (AMP)-activated protein kinase (AMPK) phosphorylation, and improving LPS induced lung injury in septic mice; the 72 h survival rate of septic mice treated with GDF7 exceeds 50% [ 27 ].…”

Growth differentiation factor 7 autocrine signaling promotes hepatic progenitor cell expansion in liver fibrosis

“…Accordingly, Zhou et al demonstrated that GDF7 promotes human adipose-derived stem cell differentiation in vitro [ 14 ]. In addition, Dong et al found that GDF7 ameliorates sepsis-induced acute lung injury by regulating the STING/AMPK pathway [ 15 ]. Interestingly, GDF7 mRNA levels in blood cells are elevated in patients with liver cirrhosis compared to healthy controls [ 16 ].…”

Retracted: Growth Differentiation Factor 7 Prevents Sepsis‐Induced Acute Lung Injury in Mice

“…This article has been retracted by Hindawi following an investigation undertaken by the publisher [ 1 ]. This investigation has uncovered evidence of one or more of the following indicators of systematic manipulation of the publication process: Discrepancies in scope Discrepancies in the description of the research reported Discrepancies between the availability of data and the research described Inappropriate citations Incoherent, meaningless and/or irrelevant content included in the article Peer-review manipulation …”

“…Tis article has been retracted by Hindawi following an investigation undertaken by the publisher [1]. Tis investigation has uncovered evidence of one or more of the following indicators of systematic manipulation of the publication process:…”