{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T18:10:02Z","timestamp":1789150202674,"version":"build-2803163510"},"reference-count":26,"publisher":"Public Library of Science (PLoS)","issue":"9","license":[{"start":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T00:00:00Z","timestamp":1789084800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Suzhou Key Discipline Project of Pediatric Immunology","award":["SZXK202106"],"award-info":[{"award-number":["SZXK202106"]}]},{"DOI":"10.13039\/100016086","name":"Key Laboratory in Science and Technology Development Project of Suzhou","doi-asserted-by":"publisher","award":["SS202067"],"award-info":[{"award-number":["SS202067"]}],"id":[{"id":"10.13039\/100016086","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS One"],"abstract":"<jats:sec id=\"sec001\">\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      Renal interstitial fibrosis and peritubular capillary (PTC) rarefaction drive the progression of chronic kidney disease (CKD). While\n                      <jats:italic>N-acetyl-seryl-aspartyl-lysyl-proline<\/jats:italic>\n                      (AcSDKP) is an endogenous anti-fibrotic peptide, its specific effects on pericyte-endothelial crosstalk and tubular epithelial survival remain controversial.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec002\">\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      We employed a self-controlled unilateral aristolochic acid (AA)-induced CKD mouse model to evaluate the time-sensitive efficacy of AcSDKP. In vitro, primary murine pericytes, human tubular epithelial cells (HK-2), and endothelial cells were utilized. Functional mechanisms were dissected using VEGF ELISA, RNA-sequencing, and targeted\n                      <jats:italic>FGFR1<\/jats:italic>\n                      siRNA knockdown.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec003\">\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      In vitro, AcSDKP potently suppressed TGF-\u03b21-induced pericyte-to-myofibroblast transition (PMT) and robustly restored pericyte-derived\n                      <jats:italic>VEGF<\/jats:italic>\n                      secretion, thereby rescuing endothelial tubulogenesis. In vivo, early AcSDKP intervention (Week 3) significantly mitigated fibrosis, preserved capillary integrity, and improved systemic renal function (BUN\/SCr), whereas late intervention (Week 4) was less effective. Transcriptomics identified the\n                      <jats:italic>VEGF\/FGFR1<\/jats:italic>\n                      axis as a primary target of AcSDKP. However, in AA-injured HK-2 cells, AcSDKP paradoxically exacerbated apoptosis despite upregulating\n                      <jats:italic>FGFR1<\/jats:italic>\n                      . Subsequent siRNA knockdown revealed that silencing\n                      <jats:italic>FGFR1<\/jats:italic>\n                      drastically worsened apoptosis, proving that endogenous\n                      <jats:italic>FGFR1<\/jats:italic>\n                      upregulation is a compensatory survival response. AcSDKP\u2019s epithelial toxicity is fundamentally\n                      <jats:italic>FGFR1<\/jats:italic>\n                      -independent, driven instead by its concurrent inhibition of the Akt survival pathway.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec004\">\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      AcSDKP exerts a compartment-specific dual role in CKD. It is a potent vascular protector that halts PMT and promotes\n                      <jats:italic>VEGF<\/jats:italic>\n                      -driven endothelial repair, but acts as a pro-apoptotic stressor in severely damaged tubules. Its clinical translation necessitates early-stage intervention and optimized delivery strategies to maximize vascular benefits while mitigating epithelial toxicity.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1371\/journal.pone.0355409","type":"journal-article","created":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T17:37:51Z","timestamp":1789148271000},"page":"e0355409","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":0,"title":["A dual role of AcSDKP in chronic kidney disease: Targeting pericyte-driven fibrosis and vascular repair via VEGF\/FGFR1 while eliciting a compensatory FGFR1 upregulation in apoptotic tubular 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