onr:"swepub:oai:gup.ub.gu.se/198414"
Search: onr:"swepub:oai:gup.ub.gu.se/198414" > Endothelial mitocho...
- 1 of 1
- Previous record
- Next record
- To hitlist
Endothelial mitochondrial oxidative stress determines podocyte depletion in segmental glomerulosclerosis
- Daehn, I. (author)
- Casalena, G. (author)
- Zhang, T. R. (author)
- show more...
- Shi, S. L. (author)
- Fenninger, F. (author)
- Barasch, N. (author)
- Yu, L. P. (author)
- D'Agati, V. (author)
- Schlondorff, D. (author)
- Kriz, W. (author)
- Bottinger, E. P. (author)
- show less...
- (creator_code:org_t)
- 2014-03-03
- 2014
- English.
- In: Journal of Clinical Investigation. - : American Society for Clinical Investigation. - 0021-9738. ; 124:4, s. 1608-1621
- Journal article (peer-reviewed)
Abstract
Subject headings
Close
- Focal segmental glomerular sclerosis (FSGS) is a primary kidney disease that is commonly associated with proteinuria and progressive loss of glomerular function, leading to development of chronic kidney disease (CKD). FSGS is characterized by podocyte injury and depletion and collapse of glomerular capillary segments. Progression of FSGS is associated with TGF-beta activation in podocytes; however, it is not clear how TGF-beta signaling promotes disease. Here, we determined that podocyte-specific activation of TGF-beta signaling in transgenic mice and BALB/c mice with Adriamycin-induced glomerulosclerosis is associated with endothelin-1 (EDN1) release by podocytes, which mediates mitochondrial oxidative stress and dysfunction in adjacent endothelial cells via paracrine EDN1 receptor type A (EDNRA) activation. Endothelial dysfunction promoted podocyte apoptosis, and inhibition of EDNRA or scavenging of mitochondrial-targeted ROS prevented podocyte loss, albuminuria, glomerulosclerosis, and renal failure. We confirmed reciprocal crosstalk between podocytes and endothelial cells in a coculture system. Biopsies from patients with FSGS exhibited increased mitochondrial DNA damage, consistent with EDNRA-mediated glomerular endothelial mitochondrial oxidative stress. Our studies indicate that segmental glomerulosclerosis develops as a result of podocyte-endothelial crosstalk mediated by EDN1/EDNRA-dependent mitochondrial dysfunction and suggest that targeting the reciprocal interaction between podocytes and endothelia may provide opportunities for therapeutic intervention in FSGS.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Endokrinologi och diabetes (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Endocrinology and Diabetes (hsv//eng)
Keyword
- GROWTH-FACTOR-BETA
- GLOMERULAR-FILTRATION BARRIER
- CHRONIC
- KIDNEY-DISEASE
- NITRIC-OXIDE SYNTHASE
- DIABETIC-NEPHROPATHY
- NADPH-OXIDASE
- TGF-BETA
- MESANGIAL CELL
- EXPRESSION
- INJURY
Publication and Content Type
- ref (subject category)
- art (subject category)
Find in a library
- Journal of Clinical Investigation (Search for host publication in LIBRIS)
To the university's database
- 1 of 1
- Previous record
- Next record
- To hitlist
Find more in SwePub
- By the author/editor
- Daehn, I.
- Casalena, G.
- Zhang, T. R.
- Shi, S. L.
- Fenninger, F.
- Barasch, N.
- show more...
- Yu, L. P.
- D'Agati, V.
- Schlondorff, D.
- Kriz, W.
- Haraldsson, Börj ...
- Bottinger, E. P.
- show less...
- About the subject
-
- MEDICAL AND HEALTH SCIENCES
- MEDICAL AND HEAL ...
- and Clinical Medicin ...
- and Endocrinology an ...
- Articles in the publication
- Journal of Clini ...
- By the university
- University of Gothenburg
Search outside SwePub
- Extend your search to:
- Google Book Search
- Google Scholar
Kungliga biblioteket hanterar dina personuppgifter i enlighet med EU:s dataskyddsförordning (2018), GDPR. Läs mer om hur det funkar här.
Så här hanterar KB dina uppgifter vid användning av denna tjänst.
- Copyright © LIBRIS - National Library Systems
- LIBRIS.kb.se
