{"title":"MFGE8在急性肺损伤中通过BMP信号通路调控hlmec的EndoMT和纤维化。","authors":"Qingqiang Shi, Huang Liu, Hanghang Wang, Ling Tang, Qi Di, Daoxin Wang","doi":"10.1186/s12931-025-03215-8","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>To investigate the effects and mechanisms of MFGE8 on LPS-induced endothelial-to-mesenchymal transition (EndoMT) and pulmonary fibrosis in human lung microvascular endothelial cells (HLMECs) and a mouse model of acute lung injury.</p><p><strong>Methods: </strong>Serum MFGE8 levels were compared between ARDS patients and controls. In vitro, HLMECs were treated with LPS, siRNA targeting MFGE8, and recombinant human MFGE8 (rhMFGE8).HLMEC morphology, invasion, migration, and EndoMT markers (CD31, ɑ-SMA) were evaluated. BMP/Smad1/5-Smad4 signaling and Snail expression were assessed via immunofluorescence, western blotting, and qRT-PCR. In vivo, rhMFGE8 effects on pulmonary fibrosis and EndoMT were analyzed in a mouse model of acute lung injury.</p><p><strong>Results: </strong>MFGE8 levels were significantly reduced in ARDS patients, with higher levels correlating to better survival. In vitro, rhMFGE8 improved HLMEC morphology, reduced invasion and migration, and attenuated LPS-induced EndoMT by increasing CD31 and decreasing α-SMA. MFGE8 knockdown increased BMP/Smad1/5-Smad4 signaling and Snail expression, while rhMFGE8 inhibited these effects. In vivo, rhMFGE8 ameliorated pulmonary fibrosis and EndoMT in mice.</p><p><strong>Conclusions: </strong>MFGE8 regulates LPS-induced EndoMT in HLMECs via the BMP/Smad1/5-Smad4 pathway and protects against pulmonary fibrosis in acute lung injury, suggesting it as a therapeutic target for ALI and ARDS.</p>","PeriodicalId":49131,"journal":{"name":"Respiratory Research","volume":"26 1","pages":"142"},"PeriodicalIF":5.8000,"publicationDate":"2025-04-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11995649/pdf/","citationCount":"0","resultStr":"{\"title\":\"MFGE8 regulates the EndoMT of HLMECs through the BMP signaling pathway and fibrosis in acute lung injury.\",\"authors\":\"Qingqiang Shi, Huang Liu, Hanghang Wang, Ling Tang, Qi Di, Daoxin Wang\",\"doi\":\"10.1186/s12931-025-03215-8\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>To investigate the effects and mechanisms of MFGE8 on LPS-induced endothelial-to-mesenchymal transition (EndoMT) and pulmonary fibrosis in human lung microvascular endothelial cells (HLMECs) and a mouse model of acute lung injury.</p><p><strong>Methods: </strong>Serum MFGE8 levels were compared between ARDS patients and controls. In vitro, HLMECs were treated with LPS, siRNA targeting MFGE8, and recombinant human MFGE8 (rhMFGE8).HLMEC morphology, invasion, migration, and EndoMT markers (CD31, ɑ-SMA) were evaluated. BMP/Smad1/5-Smad4 signaling and Snail expression were assessed via immunofluorescence, western blotting, and qRT-PCR. In vivo, rhMFGE8 effects on pulmonary fibrosis and EndoMT were analyzed in a mouse model of acute lung injury.</p><p><strong>Results: </strong>MFGE8 levels were significantly reduced in ARDS patients, with higher levels correlating to better survival. In vitro, rhMFGE8 improved HLMEC morphology, reduced invasion and migration, and attenuated LPS-induced EndoMT by increasing CD31 and decreasing α-SMA. MFGE8 knockdown increased BMP/Smad1/5-Smad4 signaling and Snail expression, while rhMFGE8 inhibited these effects. In vivo, rhMFGE8 ameliorated pulmonary fibrosis and EndoMT in mice.</p><p><strong>Conclusions: </strong>MFGE8 regulates LPS-induced EndoMT in HLMECs via the BMP/Smad1/5-Smad4 pathway and protects against pulmonary fibrosis in acute lung injury, suggesting it as a therapeutic target for ALI and ARDS.</p>\",\"PeriodicalId\":49131,\"journal\":{\"name\":\"Respiratory Research\",\"volume\":\"26 1\",\"pages\":\"142\"},\"PeriodicalIF\":5.8000,\"publicationDate\":\"2025-04-13\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11995649/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Respiratory Research\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1186/s12931-025-03215-8\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"Medicine\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Respiratory Research","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1186/s12931-025-03215-8","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"Medicine","Score":null,"Total":0}
MFGE8 regulates the EndoMT of HLMECs through the BMP signaling pathway and fibrosis in acute lung injury.
Background: To investigate the effects and mechanisms of MFGE8 on LPS-induced endothelial-to-mesenchymal transition (EndoMT) and pulmonary fibrosis in human lung microvascular endothelial cells (HLMECs) and a mouse model of acute lung injury.
Methods: Serum MFGE8 levels were compared between ARDS patients and controls. In vitro, HLMECs were treated with LPS, siRNA targeting MFGE8, and recombinant human MFGE8 (rhMFGE8).HLMEC morphology, invasion, migration, and EndoMT markers (CD31, ɑ-SMA) were evaluated. BMP/Smad1/5-Smad4 signaling and Snail expression were assessed via immunofluorescence, western blotting, and qRT-PCR. In vivo, rhMFGE8 effects on pulmonary fibrosis and EndoMT were analyzed in a mouse model of acute lung injury.
Results: MFGE8 levels were significantly reduced in ARDS patients, with higher levels correlating to better survival. In vitro, rhMFGE8 improved HLMEC morphology, reduced invasion and migration, and attenuated LPS-induced EndoMT by increasing CD31 and decreasing α-SMA. MFGE8 knockdown increased BMP/Smad1/5-Smad4 signaling and Snail expression, while rhMFGE8 inhibited these effects. In vivo, rhMFGE8 ameliorated pulmonary fibrosis and EndoMT in mice.
Conclusions: MFGE8 regulates LPS-induced EndoMT in HLMECs via the BMP/Smad1/5-Smad4 pathway and protects against pulmonary fibrosis in acute lung injury, suggesting it as a therapeutic target for ALI and ARDS.
期刊介绍：
Respiratory Research publishes high-quality clinical and basic research, review and commentary articles on all aspects of respiratory medicine and related diseases.
As the leading fully open access journal in the field, Respiratory Research provides an essential resource for pulmonologists, allergists, immunologists and other physicians, researchers, healthcare workers and medical students with worldwide dissemination of articles resulting in high visibility and generating international discussion.
Topics of specific interest include asthma, chronic obstructive pulmonary disease, cystic fibrosis, genetics, infectious diseases, interstitial lung diseases, lung development, lung tumors, occupational and environmental factors, pulmonary circulation, pulmonary pharmacology and therapeutics, respiratory immunology, respiratory physiology, and sleep-related respiratory problems.
求助内容：
应助结果提醒方式：
京公网安备 11010802042870号
