{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T14:02:04Z","timestamp":1785420124996,"version":"3.56.0"},"reference-count":37,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2026,6,16]],"date-time":"2026-06-16T00:00:00Z","timestamp":1781568000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82370732"],"award-info":[{"award-number":["82370732"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"award":["82370732"],"award-info":[{"award-number":["82370732"]}],"id":[{"id":"https:\/\/ror.org\/01h0zpd94","id-type":"ROR","asserted-by":"publisher"}]},{"name":"Guidance Funds of the Central Government for Local Science and Technology","award":["236Z7739G"],"award-info":[{"award-number":["236Z7739G"]}]},{"name":"Director\u2019s Fund of the Key Laboratory of Forensic Medicine of Hebei Province","award":["JYFY-23ZR014"],"award-info":[{"award-number":["JYFY-23ZR014"]}]},{"DOI":"10.13039\/501100003787","name":"Natural Science Foundation of Hebei Province","doi-asserted-by":"publisher","award":["H2025206723"],"award-info":[{"award-number":["H2025206723"]}],"id":[{"id":"10.13039\/501100003787","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Science Research Project of Hebei Education Department","award":["QN2023040"],"award-info":[{"award-number":["QN2023040"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Tubulointerstitial fibrosis (TIF) represents the final common pathway leading to end-stage renal disease (ESRD) in chronic kidney disease (CKD). Despite fibrosis being well established as a key pathological hallmark, the molecular mediators that drive this process remain incompletely understood. BPI fold-containing family A member 2 (BPIFA2), a secreted innate immune protein of the sPLUNC family, was upregulated in renal tubular epithelial cells across diverse CKD etiologies and strongly correlated with collagen I accumulation and TIF severity. Tubule-specific knockdown of BPIFA2 significantly alleviated renal histopathological injury and fibrosis, whereas exogenous BPIFA2 administration aggravated fibrotic progression. Mechanistically, BPIFA2 promoted epithelial\u2013mesenchymal transition (EMT) in tubular epithelial cells and triggered macrophage-to-myofibroblast transition (MMT) associated with the TGF-\u03b2\/Smad3 signaling pathway. In conclusion, our findings identify BPIFA2 as a novel profibrotic mediator in CKD. Targeting BPIFA2 or its downstream signaling may offer new therapeutic opportunities for chronic kidney disease.<\/jats:p>","DOI":"10.3390\/cells15121093","type":"journal-article","created":{"date-parts":[[2026,6,16]],"date-time":"2026-06-16T09:06:52Z","timestamp":1781600812000},"page":"1093","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["BPIFA2 Promotes Renal Fibrosis by Regulating Tubular Epithelial-to-Mesenchymal Transition and Macrophage Activation in Chronic Kidney Disease"],"prefix":"10.3390","volume":"15","author":[{"given":"Xinyan","family":"Miao","sequence":"first","affiliation":[{"name":"Key Laboratory of Kidney Diseases of Hebei Province, Department of Pathology, Center of Metabolic Diseases and Cancer Research, Institute of Medical and Health Science, Hebei Medical University, Shijiazhuang 050017, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zecheng","family":"Lu","sequence":"additional","affiliation":[{"name":"Key Laboratory of Kidney Diseases of Hebei Province, Department of Pathology, Center of Metabolic Diseases and Cancer Research, Institute of Medical and Health Science, Hebei Medical University, Shijiazhuang 050017, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoqi","family":"Xing","sequence":"additional","affiliation":[{"name":"Key Laboratory of Kidney Diseases of Hebei Province, Department of Pathology, Center of Metabolic Diseases and Cancer Research, Institute of Medical and Health Science, Hebei Medical University, Shijiazhuang 050017, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuexin","family":"Tian","sequence":"additional","affiliation":[{"name":"Key Laboratory of Kidney Diseases of Hebei Province, Department of Pathology, Center of Metabolic Diseases and Cancer Research, Institute of Medical and Health Science, Hebei Medical University, Shijiazhuang 050017, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinxi","family":"Liu","sequence":"additional","affiliation":[{"name":"Key Laboratory of Kidney Diseases of Hebei Province, Department of Pathology, Center of Metabolic Diseases and Cancer Research, Institute of Medical and Health Science, Hebei Medical University, Shijiazhuang 050017, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Zhang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Kidney Diseases of Hebei Province, Department of Pathology, Center of Metabolic Diseases and Cancer Research, Institute of Medical and Health Science, Hebei Medical University, Shijiazhuang 050017, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1795-9368","authenticated-orcid":false,"given":"Qingjuan","family":"Liu","sequence":"additional","affiliation":[{"name":"Key Laboratory of Kidney Diseases of Hebei Province, Department of Pathology, Center of Metabolic Diseases and Cancer Research, Institute of Medical and Health Science, Hebei Medical University, Shijiazhuang 050017, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaojuan","family":"Feng","sequence":"additional","affiliation":[{"name":"Key Laboratory of Kidney Diseases of Hebei Province, Department of Pathology, Center of Metabolic Diseases and Cancer Research, Institute of Medical and Health Science, Hebei Medical University, Shijiazhuang 050017, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuxia","family":"Liu","sequence":"additional","affiliation":[{"name":"Key Laboratory of Kidney Diseases of Hebei Province, Department of Pathology, Center of Metabolic Diseases and Cancer Research, Institute of Medical and Health Science, Hebei Medical University, Shijiazhuang 050017, China"},{"name":"Hebei University of Engineering, Handan 056038, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,6,16]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"(2024). 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