{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T08:39:20Z","timestamp":1791362360589,"version":"4.3.1"},"reference-count":53,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,2,5]],"date-time":"2026-02-05T00:00:00Z","timestamp":1770249600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Inflammation-driven fibrosis represents a common pathological endpoint in both heart failure (HF) and chronic kidney disease (CKD), which together affect over 1 billion people worldwide. Understanding the shared molecular mechanisms by which inflammation contributes to the pathogenesis of HF and CKD is crucial for enabling early diagnosis and guiding the development of broad-spectrum therapeutic strategies.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Utilizing multi-omics technologies and machine learning algorithms, we performed an integrative analysis of HF and CKD samples to uncover shared mechanisms underlying inflammation-induced fibrosis. Furthermore, key regulators identified through bioinformatic analysis were experimentally validated using primary cell co-culture assays, gene knockout approaches, and bulk RNA sequencing.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Single-nucleus RNA sequencing (snRNA-seq) revealed concurrent upregulation of IL-1\u03b2 and Pleckstrin Homology-Like Domain Family A Member 1 (PHLDA1) in both cardiac M1 macrophages and injured proximal tubular epithelial (PTE) cells. PHLDA1 promotes IL-1\u03b2 expression and the knockout of PHLDA1 suppressed NF-\u03baB signaling and renal fibrosis. Administration of IL-1\u03b2 induced PHLDA1 expression in cardiac fibroblasts and renal PDGFR\u03b2\n                      <jats:sup>+<\/jats:sup>\n                      cells, suggesting a positive feedback loop that contributes to fibrosis.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>In this study, we identified PHLDA1 as a key driver of fibrosis in both the heart and kidney, acting through IL-1\u03b2 mediated intercellular crosstalk. These findings indicate PHLDA1 as a potential therapeutic candidate for mitigating fibrosis in cardio-renal syndrome.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2026.1765221","type":"journal-article","created":{"date-parts":[[2026,2,5]],"date-time":"2026-02-05T11:15:55Z","timestamp":1770290155000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["PHLDA1 is a shared diagnostic and key mediator of inflammatory fibrosis in heart and kidney"],"prefix":"10.3389","volume":"17","author":[{"given":"Lei","family":"Hua","sequence":"first","affiliation":[{"name":"Department of Nephrology and Rheumatology Immunology, Ningbo Medical Centre Lihuili Hospital","place":["Ningbo, Zhejiang, China"]},{"name":"Department of Cardiovascular Medicine, The First Affiliated Hospital of Nanjing Medical University","place":["Nanjing, Jiangsu, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liangru","family":"Shen","sequence":"additional","affiliation":[{"name":"Department of Nephrology, Kang Shen Hospital, the Affiliated Hospital of Jiangsu Food & Pharmaceutical Science College","place":["Suqian, Jiangsu, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yongshou","family":"Tao","sequence":"additional","affiliation":[{"name":"Baicheng County Maternal and Child Healthcare Hospital","place":["Aksu, Xinjiang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chentong","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Nephrology and Rheumatology Immunology, Ningbo Medical Centre Lihuili Hospital","place":["Ningbo, Zhejiang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaohang","family":"Shao","sequence":"additional","affiliation":[{"name":"Department of Nephrology and Rheumatology Immunology, Ningbo 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