Upregulation of Matrix Metalloproteinase-9 Protects against Sepsis-Induced Acute Lung Injury via Promoting the Release of Soluble Receptor for Advanced Glycation End Products.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:33628393", "kind": "science-record", "revision": 8, "content_hash": "sha256:7e39d1a6b3728df20d4192fe52b785a7d39a7f361289ef7f5e78afb5e3e96c68", "created_at": "2026-11-01T15:41:26Z", "updated_at": "2026-11-01T22:46:11Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Upregulation of Matrix Metalloproteinase-9 Protects against Sepsis-Induced Acute Lung Injury via Promoting the Release of Soluble Receptor for Advanced Glycation End Products.", "doi": "10.1155/2021/8889313", "pmid": "33628393", "authors": ["Hui Zhang", "Yan-Fei Mao", "Ying Zhao", "Dun-Feng Xu", "Yan Wang", "Chu-Fan Xu", "Wen-Wen Dong", "Xiao-Yan Zhu", "Ning Ding", "Lai Jiang", "Yu-Jian Liu"], "journal": "Oxidative medicine and cellular longevity", "year": 2021, "abstract": "Dysregulation of matrix metalloproteinase- (MMP-) 9 is implicated in the pathogenesis of acute lung injury (ALI). However, it remains controversial whether MMP-9 improves or deteriorates acute lung injury of different etiologies. The receptor for advanced glycation end products (RAGE) plays a critical role in the pathogenesis of acute lung injury. MMPs are known to mediate RAGE shedding and release of soluble RAGE (sRAGE), which can act as a decoy receptor by competitively inhibiting the binding of RAGE ligands to RAGE. Therefore, this study is aimed at clarifying whether and how pulmonary knockdown of MMP-9 affected sepsis-induced acute lung injury as well as the release of sRAGE in a murine cecal ligation and puncture (CLP) model. The analysis of GEO mouse sepsis datasets GSE15379, GSE52474, and GSE60088 revealed that the mRNA expression of MMP-9 was significantly upregulated in septic mouse lung tissues. Elevation of pulmonary MMP-9 mRNA and protein expressions was confirmed in CLP-induced mouse sepsis model. Intratracheal injection of MMP-9 siRNA resulted in an approximately 60% decrease in pulmonary MMP-9 expression. It was found that pulmonary knockdown of MMP-9 significantly increased mortality of sepsis and exacerbated sepsis-associated acute lung injury. Pulmonary MMP-9 knockdown also decreased sRAGE release and enhanced sepsis-induced activation of the RAGE/nuclear factor-κB (NF-κB) signaling pathway, meanwhile aggravating sepsis-induced oxidative stress and inflammation in lung tissues. In addition, administration of recombinant sRAGE protein suppressed the activation of the RAGE/NF-κB signaling pathway and ameliorated pulmonary oxidative stress, inflammation, and lung injury in CLP-induced septic mice. In conclusion, our data indicate that MMP-9-mediated RAGE shedding limits the severity of sepsis-associated pulmonary edema, inflammation, oxidative stress, and lung injury by suppressing the RAGE/NF-κB signaling pathway via the decoy receptor activities of sRAGE. MMP-9-mediated sRAGE production may serve as a self-limiting mechanism to control and resolve excessive inflammation and oxidative stress in the lung during sepsis.", "claims": [{"id": "claim-method", "statement": "Statistical significance in experiments comparing only two groups was determined by two-tailed Student's t-test. The comparison among multiple groups was estimated by one-way analysis of variance followed by post hoc analysis using Student-Newman-Keuls test. To determine statistical significance between survival curves, the Kaplan–Meier test was used. All raw data will be available upon request to the corresponding author from this manuscript.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:33628393", "locator": "sections[13] \"2.11. 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