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Here, we studied the molecular mechanisms of kidney iron loading in experimental focal segmental glomerulosclerosis (FSGS) and investigated the effect of iron-reducing interventions on disease progression. Thy-1.1 mice were injected with anti-Thy-1.1 monoclonal antibody (mAb) to induce proteinuria. Urine, blood and tissue were collected at day (D)1, D5, D8, D15 and D22 after mAb injection. Thy-1.1 mice were subjected to captopril (CA), iron-deficient (ID) diet or iron chelation (deferoxamine; DFO). MAb injection resulted in significant albuminuria at all time points (p\u2009&lt;\u20090.01). Kidney iron loading, predominantly in distal tubules, increased in time, along with urinary kidney injury molecule-1 and 24p3 concentration, as well as kidney mRNA expression of <jats:italic>Interleukin-6<\/jats:italic> (<jats:italic>Il-6)<\/jats:italic> and <jats:italic>Heme oxygenase-1<\/jats:italic> (<jats:italic>Ho-1)<\/jats:italic>. Treatment with CA, ID diet or DFO significantly reduced kidney iron deposition at D8 and D22 (p\u2009&lt;\u20090.001) and fibrosis at D22 (p\u2009&lt;\u20090.05), but not kidney <jats:italic>Il-6<\/jats:italic>. ID treatment increased kidney <jats:italic>Ho-1<\/jats:italic> (p\u2009&lt;\u20090.001). In conclusion, kidney iron accumulation coincides with progression of tubulointerstitial injury in this model of FSGS. Reduction of iron loading halts disease progression. However, targeted approaches to prevent excessive kidney iron loading are warranted to maintain the delicate systemic and cellular iron balance.<\/jats:p>","DOI":"10.1038\/s41598-022-05261-4","type":"journal-article","created":{"date-parts":[[2022,1,24]],"date-time":"2022-01-24T11:03:57Z","timestamp":1643022237000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Kidney tubule iron loading in experimental focal segmental glomerulosclerosis"],"prefix":"10.1038","volume":"12","author":[{"given":"Rachel P. L.","family":"van Swelm","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sanne","family":"Beurskens","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Henry","family":"Dijkman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erwin T. 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