{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,4]],"date-time":"2026-11-04T17:37:24Z","timestamp":1793813844655,"version":"4.6.1"},"reference-count":47,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,1,30]],"date-time":"2026-01-30T00:00:00Z","timestamp":1769731200000},"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. Pharmacol."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>\n                      Obstructive nephropathy is a major cause of chronic kidney disease (CKD), characterized by progressive renal fibrosis with limited treatment options. CD206\n                      <jats:sup>+<\/jats:sup>\n                      macrophages have emerged as key drivers of fibrogenesis, yet targeted strategies against this subset remain undeveloped.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Using human ureteropelvic junction obstruction (UPJO) tissues and a murine unilateral ureteral obstruction (UUO) model, we assessed the accumulation of CD206\n                      <jats:sup>+<\/jats:sup>\n                      macrophages and the progression of fibrosis. The therapeutic peptide RP-182, which selectively targets CD206, was administered daily to UUO mice. Histological, molecular, and flow cytometric analyses were performed to evaluate renal injury, fibrosis, inflammation, and macrophage polarization.\n                      <jats:italic>In vitro<\/jats:italic>\n                      studies using bone marrow-derived macrophages elucidated the mechanisms underlying the action of RP-182.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      CD206\n                      <jats:sup>+<\/jats:sup>\n                      macrophages were significantly enriched in human UPJO kidneys and UUO mice, correlating with fibrosis severity. RP-182 treatment attenuated collagen deposition, \u03b1- SMA expression, tubular damage, and inflammatory cell infiltration in UUO kidneys.\n                      <jats:italic>In vitro<\/jats:italic>\n                      , RP-182 selectively inhibited IL-4\/IL-13-induced M2 polarization and suppressed TGF- \u03b2-triggered macrophage-to-myofibroblast transition (MMT) in M2 macrophages, while sparing M1 responses. Mechanistically, RP-182 downregulated \u03b2-catenin signaling, a pathway crucial for M2 programming and MMT.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>\n                      Our findings demonstrate that RP-182 alleviates obstructive renal fibrosis by specifically targeting CD206\n                      <jats:sup>+<\/jats:sup>\n                      macrophages, inhibiting their M2 polarization and MMT via \u03b2-catenin suppression. This work highlights RP-182 as a novel macrophage- directed therapeutic candidate for progressive kidney fibrosis.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fphar.2026.1739457","type":"journal-article","created":{"date-parts":[[2026,1,30]],"date-time":"2026-01-30T05:26:32Z","timestamp":1769750792000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":8,"title":["RP-182 alleviated obstruction-induced renal fibrosis by reprogramming CD206+ macrophages"],"prefix":"10.3389","volume":"17","author":[{"given":"Hualin","family":"Cao","sequence":"first","affiliation":[{"name":"Department of Urology, The First Affiliated Hospital of Guangxi Medical University","place":["Nanning, China"]},{"name":"Nanxishan Hospital (The Second People\u2019s Hospital) of Guangxi Zhuang Autonomous Region","place":["Guilin, 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