{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T02:24:13Z","timestamp":1790389453289,"version":"4.1.0"},"reference-count":55,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"12","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JASN"],"published-print":{"date-parts":[[2017,12]]},"abstract":"<jats:p>\n                    Renal fibrosis is a common underlying process of progressive kidney diseases. We investigated the role of macrophage migration inhibitory factor (MIF), a pleiotropic proinflammatory cytokine, in this process. In mice subjected to unilateral ureteral obstruction, genetic deletion or pharmacologic inhibition of MIF aggravated fibrosis and inflammation, whereas treatment with recombinant MIF was beneficial, even in established fibrosis. In two other models of progressive kidney disease, global\n                    <jats:italic toggle=\"yes\">Mif<\/jats:italic>\n                    deletion or MIF inhibition also worsened fibrosis and inflammation and associated with worse kidney function. Renal MIF expression was reduced in tubular cells in fibrotic compared with healthy murine and human kidneys. Bone marrow chimeras showed that\n                    <jats:italic toggle=\"yes\">Mif<\/jats:italic>\n                    expression in bone marrow-derived cells did not affect fibrosis and inflammation after UUO. However,\n                    <jats:italic toggle=\"yes\">Mif<\/jats:italic>\n                    gene deletion restricted to renal tubular epithelial cells aggravated these effects. In LPS-stimulated tubular cell cultures,\n                    <jats:italic toggle=\"yes\">Mif<\/jats:italic>\n                    deletion led to enhanced G2\/M cell-cycle arrest and increased expression of the CDK inhibitor 1B (p27Kip1) and of proinflammatory and profibrotic mediators. Furthermore, MIF inhibition reduced tubular cell proliferation\n                    <jats:italic toggle=\"yes\">in vitro<\/jats:italic>\n                    . In all three\n                    <jats:italic toggle=\"yes\">in vivo<\/jats:italic>\n                    models, global\n                    <jats:italic toggle=\"yes\">Mif<\/jats:italic>\n                    deletion or MIF inhibition caused similar effects and attenuated the expression of cyclin B1 in tubular cells.\n                    <jats:italic toggle=\"yes\">Mif<\/jats:italic>\n                    deletion also resulted in reduced tubular cell apoptosis after UUO. Recombinant MIF exerted opposing effects on tubular cells\n                    <jats:italic toggle=\"yes\">in vitro<\/jats:italic>\n                    and\n                    <jats:italic toggle=\"yes\">in vivo<\/jats:italic>\n                    . Our data identify renal tubular MIF as an endogenous renoprotective factor in progressive kidney diseases, raising the possibility of pharmacologic intervention with MIF pathway agonists, which are in advanced preclinical development.\n                  <\/jats:p>","DOI":"10.1681\/asn.2017020190","type":"journal-article","created":{"date-parts":[[2017,8,11]],"date-time":"2017-08-11T20:30:23Z","timestamp":1502483423000},"page":"3590-3604","source":"Crossref","is-referenced-by-count":76,"title":["Macrophage Migration Inhibitory Factor Limits Renal Inflammation and Fibrosis by Counteracting Tubular Cell Cycle Arrest"],"prefix":"10.1681","volume":"28","author":[{"given":"Sonja","family":"Djudjaj","sequence":"first","affiliation":[{"name":"Pathology and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ina V.","family":"Martin","sequence":"additional","affiliation":[{"name":"Nephrology and Immunology, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eva M.","family":"Buhl","sequence":"additional","affiliation":[{"name":"Pathology and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nina J.","family":"Nothofer","sequence":"additional","affiliation":[{"name":"Pathology and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lin","family":"Leng","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Yale University School of Medicine, New Haven, Connecticut;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marta","family":"Piecychna","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Yale University School of Medicine, New Haven, Connecticut;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J\u00fcrgen","family":"Floege","sequence":"additional","affiliation":[{"name":"Nephrology and Immunology, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J\u00fcrgen","family":"Bernhagen","sequence":"additional","affiliation":[{"name":"Institute of Biochemistry and Molecular Cell Biology, Rheinish-Westphalian Technical University, Aachen University, Aachen, Germany;"},{"name":"Department of Vascular Biology, Institute for Stroke and Dementia Research, Munich University Hospital, Ludwig-Maximilians-University, Munich, Germany; and"},{"name":"German Center for Cardiovascular Research, Munich Heart Alliance, Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard","family":"Bucala","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Yale University School of Medicine, New Haven, Connecticut;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Boor","sequence":"additional","affiliation":[{"name":"Pathology and"},{"name":"Nephrology and Immunology, 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