{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,30]],"date-time":"2026-08-30T01:55:04Z","timestamp":1788054904222,"version":"build-2784847793"},"reference-count":57,"publisher":"MDPI AG","issue":"17","license":[{"start":{"date-parts":[[2021,9,1]],"date-time":"2021-09-01T00:00:00Z","timestamp":1630454400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Our understanding of the mechanisms responsible for the progression of chronic kidney disease (CKD) is incomplete. Microarray analysis of kidneys at 4 and 7 weeks of age in Col4a3-\/- mice, a model of progressive nephropathy characterized by proteinuria, interstitial fibrosis, and inflammation, revealed that Follistatin-like-1 (Fstl1) was one of only four genes significantly overexpressed at 4 weeks of age. mRNA levels for the Fstl1 receptors, Tlr4 and Dip2a, increased in both Col4a-\/- mice and mice subjected to unilateral ureteral obstruction (UUO). RNAscope\u00ae (Advanced Cell Diagnostics, Newark CA, USA) localized Fstl1 to interstitial cells, and in silico analysis of single cell transcriptomic data from human kidneys showed Fstl1 confined to interstitial fibroblasts\/myofibroblasts. In vitro, FSTL1 activated AP1 and NF\u03baB, increased collagen I (COL1A1) and interleukin-6 (IL6) expression, and induced apoptosis in cultured kidney cells. FSTL1 expression in the NEPTUNE cohort of humans with focal segmental glomerulosclerosis (FSGS), membranous nephropathy (MN), and IgA nephropathy (IgAN) was positively associated with age, eGFR, and proteinuria by multiple linear regression, as well as with interstitial fibrosis and tubular atrophy. Clinical disease progression, defined as dialysis or a 40 percent reduction in eGFR, was greater in patients with high baseline FSTL1 mRNA levels. FSTL1 is a fibroblast-derived cytokine linked to the progression of experimental and clinical CKD.<\/jats:p>","DOI":"10.3390\/ijms22179513","type":"journal-article","created":{"date-parts":[[2021,9,1]],"date-time":"2021-09-01T11:39:03Z","timestamp":1630496343000},"page":"9513","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["Follistatin-Like-1 (FSTL1) Is a Fibroblast-Derived Growth Factor That Contributes to Progression of Chronic Kidney Disease"],"prefix":"10.3390","volume":"22","author":[{"given":"Nicholas A.","family":"Maksimowski","sequence":"first","affiliation":[{"name":"Institute of Medical Science, University of Toronto, Toronto, ON M5S 1A8, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-4130-4136","authenticated-orcid":false,"given":"Xuewen","family":"Song","sequence":"additional","affiliation":[{"name":"Division of Nephrology, University Health Network, Toronto, ON M5G 2C4, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1727-2822","authenticated-orcid":false,"given":"Eun Hui","family":"Bae","sequence":"additional","affiliation":[{"name":"Departments of Internal Medicine, Chonnam National University Medical School, Gwangju 61469, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heather","family":"Reich","sequence":"additional","affiliation":[{"name":"Division of Nephrology, University Health Network, Toronto, ON M5G 2C4, Canada"},{"name":"Toronto General Hospital Research Institute, University Health Network, Toronto, ON M5G 2C4, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rohan","family":"John","sequence":"additional","affiliation":[{"name":"Toronto General Hospital Research Institute, University Health Network, Toronto, ON M5G 2C4, Canada"},{"name":"Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON M5G 2C4, Canada"},{"name":"Department of Pathology, University Health Network, Toronto, ON M5G 2C4, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"York","family":"Pei","sequence":"additional","affiliation":[{"name":"Institute of Medical Science, University of Toronto, Toronto, ON M5S 1A8, Canada"},{"name":"Division of Nephrology, University Health Network, Toronto, ON M5G 2C4, Canada"},{"name":"Toronto General Hospital Research Institute, University Health Network, Toronto, ON M5G 2C4, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James W.","family":"Scholey","sequence":"additional","affiliation":[{"name":"Institute of Medical Science, University of Toronto, Toronto, ON M5S 1A8, Canada"},{"name":"Division of Nephrology, University Health Network, Toronto, ON M5G 2C4, Canada"},{"name":"Toronto General Hospital Research Institute, University Health Network, Toronto, ON M5G 2C4, Canada"},{"name":"Department of Pathology, University Health Network, Toronto, ON M5G 2C4, Canada"},{"name":"Department of Physiology, University of Toronto, Toronto, ON M5G 2C4, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"Nephrotic Syndrome Study Network (NEPTUNE)","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,9,1]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"3719","DOI":"10.2174\/0929867325666180307110908","article-title":"Chronic Kidney Disease and the Search for New Biomarkers for Early Diagnosis","volume":"25","author":"Saucedo","year":"2018","journal-title":"Curr. 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