{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,30]],"date-time":"2026-10-30T02:02:31Z","timestamp":1793325751539,"version":"4.5.0"},"reference-count":39,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"10","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JASN"],"published-print":{"date-parts":[[2018,10]]},"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      In patients with autosomal dominant polycystic kidney disease (ADPKD), most of whom have a mutation in\n                      <jats:italic toggle=\"yes\">PKD1<\/jats:italic>\n                      or\n                      <jats:italic toggle=\"yes\">PKD2<\/jats:italic>\n                      , abnormally large numbers of macrophages accumulate around kidney cysts and promote their growth. Research by us and others has suggested that monocyte chemoattractant protein-1 (Mcp1) may be a signal for macrophage-mediated cyst growth.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      To define the role of Mcp1 and macrophages in promoting cyst growth, we used mice with inducible knockout of\n                      <jats:italic toggle=\"yes\">Pkd1<\/jats:italic>\n                      alone (single knockout) or knockout of both\n                      <jats:italic toggle=\"yes\">Pkd1<\/jats:italic>\n                      and\n                      <jats:italic toggle=\"yes\">Mcp1<\/jats:italic>\n                      (double knockout) in the murine renal tubule. Levels of\n                      <jats:italic toggle=\"yes\">Mcp1<\/jats:italic>\n                      RNA expression were measured in single-knockout mice and controls.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      In single-knockout mice, upregulation of\n                      <jats:italic toggle=\"yes\">Mcp1<\/jats:italic>\n                      precedes macrophage infiltration. Macrophages accumulating around nascent cysts (0\u20132 weeks after induction) are initially proinflammatory and induce tubular cell injury with morphologic flattening, oxidative DNA damage, and proliferation-independent cystic dilation. At 2\u20136 weeks after induction, macrophages switch to an alternative activation phenotype and promote further cyst growth because of an additional three-fold increase in tubular cell proliferative rates. In double-knockout mice, there is a marked reduction in\n                      <jats:italic toggle=\"yes\">Mcp1<\/jats:italic>\n                      expression and macrophage numbers, resulting in less initial tubular cell injury, slower cyst growth, and improved renal function. Treatment of single-knockout mice with an inhibitor to the Mcp1 receptor Ccr2 partially reproduced the morphologic and functional improvement seen with\n                      <jats:italic toggle=\"yes\">Mcp1<\/jats:italic>\n                      knockout.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      Mcp1 is upregulated after knockout of\n                      <jats:italic toggle=\"yes\">Pkd1<\/jats:italic>\n                      and promotes macrophage accumulation and cyst growth\n                      <jats:italic toggle=\"yes\">via<\/jats:italic>\n                      both proliferation-independent and proliferation-dependent mechanisms in this orthologous mouse model of ADPKD.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1681\/asn.2018050518","type":"journal-article","created":{"date-parts":[[2018,9,12]],"date-time":"2018-09-12T14:35:15Z","timestamp":1536762915000},"page":"2471-2481","source":"Crossref","is-referenced-by-count":109,"title":["Mcp1 Promotes Macrophage-Dependent Cyst Expansion in Autosomal Dominant Polycystic Kidney Disease"],"prefix":"10.1681","volume":"29","author":[{"given":"Marcelo F.","family":"Cassini","sequence":"first","affiliation":[{"name":"Section of Nephrology, Department of Medicine,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vijayakumar R.","family":"Kakade","sequence":"additional","affiliation":[{"name":"Section of Nephrology, Department of Medicine,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth","family":"Kurtz","sequence":"additional","affiliation":[{"name":"Section of Nephrology, Department of 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