GDF-15 suppresses puromycin aminonucleoside-induced podocyte injury by reducing endoplasmic reticulum stress and glomerular inflammation

2024
journal article
article
dc.abstract.enGDF15, 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–creatinine 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.
dc.affiliationWydział Biochemii, Biofizyki i Biotechnologii : Zakład Mikrobiologii
dc.contributor.authorvon Rauchhaupt, Ekaterina
dc.contributor.authorKlaus, Martin
dc.contributor.authorRibeiro, Andrea
dc.contributor.authorHonarpisheh, Mohsen
dc.contributor.authorLi, Chenyu
dc.contributor.authorLiu, Min
dc.contributor.authorKöhler, Paulina
dc.contributor.authorAdamowicz, Karina - 186815
dc.contributor.authorSchmaderer, Christoph
dc.contributor.authorLindenmeyer, Maja
dc.contributor.authorSteiger, Stefanie
dc.contributor.authorAnders, Hans-Joachim
dc.contributor.authorLech, Maciej
dc.date.accessioned2024-05-08T12:36:26Z
dc.date.available2024-05-08T12:36:26Z
dc.date.issued2024
dc.date.openaccess0
dc.description.accesstimew momencie opublikowania
dc.description.additionalBibliogr.
dc.description.number7
dc.description.versionostateczna wersja wydawcy
dc.description.volume13
dc.identifier.articleid637
dc.identifier.doi10.3390/cells13070637
dc.identifier.eissn2073-4409
dc.identifier.urihttps://ruj.uj.edu.pl/handle/item/338862
dc.languageeng
dc.language.containereng
dc.rightsUdzielam licencji. Uznanie autorstwa 4.0 Międzynarodowa
dc.rights.licenceCC-BY
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/legalcode.pl
dc.share.typeotwarte czasopismo
dc.subject.enGDF15
dc.subject.enpodocytes
dc.subject.enendoplasmic reticulum stress
dc.subject.enpodocytopathies
dc.subject.englomerular inflammation
dc.subtypeArticle
dc.titleGDF-15 suppresses puromycin aminonucleoside-induced podocyte injury by reducing endoplasmic reticulum stress and glomerular inflammation
dc.title.journalCells
dc.typeJournalArticle
dspace.entity.typePublicationen
dc.abstract.en
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–creatinine 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.
dc.affiliation
Wydział Biochemii, Biofizyki i Biotechnologii : Zakład Mikrobiologii
dc.contributor.author
von Rauchhaupt, Ekaterina
dc.contributor.author
Klaus, Martin
dc.contributor.author
Ribeiro, Andrea
dc.contributor.author
Honarpisheh, Mohsen
dc.contributor.author
Li, Chenyu
dc.contributor.author
Liu, Min
dc.contributor.author
Köhler, Paulina
dc.contributor.author
Adamowicz, Karina - 186815
dc.contributor.author
Schmaderer, Christoph
dc.contributor.author
Lindenmeyer, Maja
dc.contributor.author
Steiger, Stefanie
dc.contributor.author
Anders, Hans-Joachim
dc.contributor.author
Lech, Maciej
dc.date.accessioned
2024-05-08T12:36:26Z
dc.date.available
2024-05-08T12:36:26Z
dc.date.issued
2024
dc.date.openaccess
0
dc.description.accesstime
w momencie opublikowania
dc.description.additional
Bibliogr.
dc.description.number
7
dc.description.version
ostateczna wersja wydawcy
dc.description.volume
13
dc.identifier.articleid
637
dc.identifier.doi
10.3390/cells13070637
dc.identifier.eissn
2073-4409
dc.identifier.uri
https://ruj.uj.edu.pl/handle/item/338862
dc.language
eng
dc.language.container
eng
dc.rights
Udzielam licencji. Uznanie autorstwa 4.0 Międzynarodowa
dc.rights.licence
CC-BY
dc.rights.uri
http://creativecommons.org/licenses/by/4.0/legalcode.pl
dc.share.type
otwarte czasopismo
dc.subject.en
GDF15
dc.subject.en
podocytes
dc.subject.en
endoplasmic reticulum stress
dc.subject.en
podocytopathies
dc.subject.en
glomerular inflammation
dc.subtype
Article
dc.title
GDF-15 suppresses puromycin aminonucleoside-induced podocyte injury by reducing endoplasmic reticulum stress and glomerular inflammation
dc.title.journal
Cells
dc.type
JournalArticle
dspace.entity.typeen
Publication
Affiliations

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