{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T04:22:18Z","timestamp":1790914938327,"version":"4.1.0"},"reference-count":74,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2024,4,5]],"date-time":"2024-04-05T00:00:00Z","timestamp":1712275200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>GDF15, also known as MIC1, is a member of the TGF-beta superfamily. Previous studies reported elevated serum levels of GDF15 in patients with kidney disorder, and its association with kidney disease progression, while other studies identified GDF15 to have protective effects. To investigate the potential protective role of GDF15 on podocytes, we first performed in vitro studies using a Gdf15-deficient podocyte cell line. The lack of GDF15 intensified puromycin aminonucleoside (PAN)-triggered endoplasmic reticulum stress and induced cell death in cultivated podocytes. This was evidenced by elevated expressions of Xbp1 and ER-associated chaperones, alongside AnnexinV\/PI staining and LDH release. Additionally, we subjected mice to nephrotoxic PAN treatment. Our observations revealed a noteworthy increase in both GDF15 expression and secretion subsequent to PAN administration. Gdf15 knockout mice displayed a moderate loss of WT1+ cells (podocytes) in the glomeruli compared to wild-type controls. However, this finding could not be substantiated through digital evaluation. The parameters of kidney function, including serum BUN, creatinine, and albumin\u2013creatinine ratio (ACR), were increased in Gdf15 knockout mice as compared to wild-type mice upon PAN treatment. This was associated with an increase in the number of glomerular macrophages, neutrophils, inflammatory cytokines, and chemokines in Gdf15-deficient mice. In summary, our findings unveil a novel renoprotective effect of GDF15 during kidney injury and inflammation by promoting podocyte survival and regulating endoplasmic reticulum stress in podocytes, and, subsequently, the infiltration of inflammatory cells via paracrine effects on surrounding glomerular cells.<\/jats:p>","DOI":"10.3390\/cells13070637","type":"journal-article","created":{"date-parts":[[2024,4,5]],"date-time":"2024-04-05T08:27:52Z","timestamp":1712305672000},"page":"637","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["GDF-15 Suppresses Puromycin Aminonucleoside-Induced Podocyte Injury by Reducing Endoplasmic Reticulum Stress and Glomerular Inflammation"],"prefix":"10.3390","volume":"13","author":[{"given":"Ekaterina","family":"von Rauchhaupt","sequence":"first","affiliation":[{"name":"Department of Medicine IV, Renal Division, Ludwig-Maximilians-University Hospital, Ludwig-Maximilians-University Munich, 80336 Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0880-3302","authenticated-orcid":false,"given":"Martin","family":"Klaus","sequence":"additional","affiliation":[{"name":"Department of Medicine IV, Renal Division, Ludwig-Maximilians-University Hospital, Ludwig-Maximilians-University Munich, 80336 Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Ribeiro","sequence":"additional","affiliation":[{"name":"Department of Medicine IV, Renal Division, Ludwig-Maximilians-University Hospital, Ludwig-Maximilians-University Munich, 80336 Munich, Germany"},{"name":"Klinikum Rechts der Isar, Department of Nephrology, Technical University Munich, 81675 Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohsen","family":"Honarpisheh","sequence":"additional","affiliation":[{"name":"Department of Medicine IV, Renal Division, Ludwig-Maximilians-University Hospital, Ludwig-Maximilians-University Munich, 80336 Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chenyu","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Medicine IV, Renal Division, Ludwig-Maximilians-University Hospital, Ludwig-Maximilians-University Munich, 80336 Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Min","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Medicine IV, Renal Division, Ludwig-Maximilians-University Hospital, Ludwig-Maximilians-University Munich, 80336 Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paulina","family":"K\u00f6hler","sequence":"additional","affiliation":[{"name":"Department of Medicine IV, Renal Division, Ludwig-Maximilians-University Hospital, Ludwig-Maximilians-University Munich, 80336 Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karina","family":"Adamowicz","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Faculty of Biochemistry, Biophysics and Biotechnology of Jagiellonian University, 30-387 Krakow, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christoph","family":"Schmaderer","sequence":"additional","affiliation":[{"name":"Klinikum Rechts der Isar, Department of Nephrology, Technical University Munich, 81675 Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maja","family":"Lindenmeyer","sequence":"additional","affiliation":[{"name":"III Department of Medicine, University Medical Center Hamburg-Eppendorf, 20251 Hamburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5990-494X","authenticated-orcid":false,"given":"Stefanie","family":"Steiger","sequence":"additional","affiliation":[{"name":"Department 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