{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T21:31:32Z","timestamp":1790803892690,"version":"4.1.0"},"reference-count":63,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2021,2,2]],"date-time":"2021-02-02T00:00:00Z","timestamp":1612224000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000062","name":"National Institute of Diabetes and Digestive and Kidney Diseases","doi-asserted-by":"publisher","award":["R01 DK075533"],"award-info":[{"award-number":["R01 DK075533"]}],"id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000062","name":"National Institute of Diabetes and Digestive and Kidney Diseases","doi-asserted-by":"publisher","award":["R01DK095059-05"],"award-info":[{"award-number":["R01DK095059-05"]}],"id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000057","name":"National Institute of General Medical Sciences","doi-asserted-by":"publisher","award":["R01 GM127701"],"award-info":[{"award-number":["R01 GM127701"]}],"id":[{"id":"10.13039\/100000057","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000057","name":"National Institute of General Medical Sciences","doi-asserted-by":"publisher","award":["U01 GM092655"],"award-info":[{"award-number":["U01 GM092655"]}],"id":[{"id":"10.13039\/100000057","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000001","name":"National Science Foundation","doi-asserted-by":"publisher","award":["DBI 1661391"],"award-info":[{"award-number":["DBI 1661391"]}],"id":[{"id":"10.13039\/100000001","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000968","name":"American Heart Association","doi-asserted-by":"publisher","award":["CDA34110287"],"award-info":[{"award-number":["CDA34110287"]}],"id":[{"id":"10.13039\/100000968","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Glucocorticoid (GC) resistance complicates the treatment of ~10\u201320% of children with nephrotic syndrome (NS), yet the molecular basis for resistance remains unclear. We used RNAseq analysis and in silico algorithm-based approaches on peripheral blood leukocytes from 12 children both at initial NS presentation and after ~7 weeks of GC therapy to identify a 12-gene panel able to differentiate steroid resistant NS (SRNS) from steroid-sensitive NS (SSNS). Among this panel, subsequent validation and analyses of one biologically relevant candidate, sulfatase 2 (SULF2), in up to a total of 66 children, revealed that both SULF2 leukocyte expression and plasma arylsulfatase activity Post\/Pre therapy ratios were greater in SSNS vs. SRNS. However, neither plasma SULF2 endosulfatase activity (measured by VEGF binding activity) nor plasma VEGF levels, distinguished SSNS from SRNS, despite VEGF\u2019s reported role as a downstream mediator of SULF2\u2019s effects in glomeruli. Experimental studies of NS-related injury in both rat glomeruli and cultured podocytes also revealed decreased SULF2 expression, which were partially reversible by GC treatment of podocytes. These findings together suggest that SULF2 levels and activity are associated with GC resistance in NS, and that SULF2 may play a protective role in NS via the modulation of downstream mediators distinct from VEGF.<\/jats:p>","DOI":"10.3390\/jcm10030523","type":"journal-article","created":{"date-parts":[[2021,2,2]],"date-time":"2021-02-02T05:44:42Z","timestamp":1612244682000},"page":"523","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Sulfatase 2 Is Associated with Steroid Resistance in Childhood Nephrotic Syndrome"],"prefix":"10.3390","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1111-9168","authenticated-orcid":false,"given":"Shipra","family":"Agrawal","sequence":"first","affiliation":[{"name":"Center for Clinical and Translational Research, Abigail Wexner Research Institute at Nationwide Children\u2019s Hospital, Columbus, OH 43205, USA"},{"name":"Department of Pediatrics, The Ohio State University College of Medicine, Columbus, OH 43210, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard","family":"Ransom","sequence":"additional","affiliation":[{"name":"Center for Clinical and Translational Research, Abigail Wexner Research Institute at Nationwide Children\u2019s Hospital, Columbus, OH 43205, USA"},{"name":"Department of Pediatrics, The Ohio State University College of Medicine, Columbus, OH 43210, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6473-1804","authenticated-orcid":false,"given":"Saras","family":"Saraswathi","sequence":"additional","affiliation":[{"name":"Battelle Center for Mathematical Medicine at Abigail Wexner Research Institute at Nationwide Children\u2019s Hospital, Columbus, OH 43205, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3194-4448","authenticated-orcid":false,"given":"Esperanza","family":"Garcia-Gonzalo","sequence":"additional","affiliation":[{"name":"Department of Mathematics, University of Oviedo, 33033 Oviedo, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amy","family":"Webb","sequence":"additional","affiliation":[{"name":"Department of Biomedical Informatics, The Ohio State University College of Medicine, Columbus, OH 43210, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4758-2832","authenticated-orcid":false,"given":"Juan","family":"Fernandez-Martinez","sequence":"additional","affiliation":[{"name":"Department of Mathematics, University of Oviedo, 33033 Oviedo, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Milan","family":"Popovic","sequence":"additional","affiliation":[{"name":"Center for Clinical and Translational Research, Abigail Wexner Research Institute at Nationwide Children\u2019s Hospital, Columbus, OH 43205, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adam","family":"Guess","sequence":"additional","affiliation":[{"name":"Center for Clinical and Translational Research, Abigail Wexner Research Institute at Nationwide Children\u2019s Hospital, Columbus, OH 43205, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1002-5095","authenticated-orcid":false,"given":"Andrzej","family":"Kloczkowski","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, The Ohio State University College of Medicine, Columbus, OH 43210, USA"},{"name":"Battelle Center for Mathematical Medicine at Abigail Wexner Research Institute at Nationwide Children\u2019s Hospital, Columbus, OH 43205, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rainer","family":"Benndorf","sequence":"additional","affiliation":[{"name":"Center for Clinical and Translational Research, Abigail Wexner Research Institute at Nationwide Children\u2019s Hospital, Columbus, OH 43205, USA"},{"name":"Department of Pediatrics, The Ohio State University College of Medicine, Columbus, OH 43210, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wolfgang","family":"Sadee","sequence":"additional","affiliation":[{"name":"Department of Cancer Biology and Genetics, Center for Pharmacogenomics, The Ohio State University College of Medicine, Columbus, OH 43210, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William","family":"Smoyer","sequence":"additional","affiliation":[{"name":"Center for Clinical and Translational Research, Abigail Wexner Research Institute at Nationwide Children\u2019s Hospital, Columbus, OH 43205, USA"},{"name":"Department of Pediatrics, The Ohio State University College of Medicine, Columbus, OH 43210, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"on behalf of the Pediatric Nephrology Research Consortium (PNRC)","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,2,2]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"445","DOI":"10.1038\/nrneph.2012.115","article-title":"Childhood nephrotic syndrome-current and future therapies","volume":"8","author":"Greenbaum","year":"2012","journal-title":"Nat. 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