{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T05:05:37Z","timestamp":1790831137723,"version":"4.1.0"},"reference-count":35,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2026,1,11]],"date-time":"2026-01-11T00:00:00Z","timestamp":1768089600000},"content-version":"vor","delay-in-days":10,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,1,1]],"date-time":"2026-01-01T00:00:00Z","timestamp":1767225600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Canadian Respiratory Journal"],"published-print":{"date-parts":[[2026,1]]},"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>The COVID\u201019 pandemic has led to a variety of long\u2010term complications, with COVID\u201019\u2010induced idiopathic pulmonary fibrosis (IPF) becoming a major concern. However, the underlying mechanisms, effective therapeutic strategies, and long\u2010term prognosis of COVID\u201019\u2010related pulmonary fibrosis remain unclear.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>This study utilized Mendelian randomization (MR) analysis and single\u2010cell RNA sequencing (scRNA\u2010seq) to systematically investigate the molecular mechanisms underlying COVID\u201019\u2010induced pulmonary fibrosis. MR analysis was conducted to assess causal relationships, while scRNA\u2010seq provided detailed insights into the cellular and molecular processes involved in fibrosis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      MR analysis revealed a significant association between COVID\u201019 infection and the development of IPF (OR\u2009=\u20091.15, 95% CI\u2009=\u20091.05\u20131.25,\n                      <jats:italic>p<\/jats:italic>\n                      = 0.001), whereas the reverse causality\u2014IPF increasing the risk of COVID\u201019 infection\u2014was not significant. Mediation analysis identified lactate metabolism as a crucial intermediary pathway in COVID\u201019\u2010induced IPF (OR\u2009=\u20091.30, 95% CI\u2009=\u20091.09\u20131.55,\n                      <jats:italic>p<\/jats:italic>\n                      = 0.003). scRNA\u2010seq confirmed the central role of lactate metabolism in pulmonary fibrosis, particularly in lung epithelial cells. The key lactate transport gene, SLC16A4, was found to play a significant role in the progression of fibrosis. Additionally, cellular interaction analysis revealed that lung epithelial cells interacted with fibroblasts via the PDGFC\u2013PDGFRA signaling axis, promoting fibrosis.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>This study uncovers a critical mechanism by which COVID\u201019 promotes pulmonary fibrosis through the regulation of lactate metabolism in lung epithelial cells, with SLC16A4 playing a pivotal role. These findings highlight the potential of targeting this metabolic pathway as a therapeutic approach for pulmonary fibrosis, offering new directions for future antifibrotic treatment strategies.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1155\/carj\/1049336","type":"journal-article","created":{"date-parts":[[2026,1,12]],"date-time":"2026-01-12T04:39:52Z","timestamp":1768192792000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Integrated Mendelian Randomization and Single\u2010Cell RNA Sequencing Analyses Reveal Lactate Metabolism as a Key Pathway in COVID\u201019\u2010Induced Pulmonary 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