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Indoxyl Sulfate Induces Renal Fibroblast Activation through a Targetable Heat Shock Protein 90-Dependent Pathway
Joint Authors
Ameri, Pietro
Verzola, Daniela
Ghigliotti, Giorgio
Milanesi, Samantha
Garibaldi, Silvano
Saio, Michela
Picciotto, Daniela
Barisione, Chiara
Garibotto, G.
Source
Oxidative Medicine and Cellular Longevity
Issue
Vol. 2019, Issue 2019 (31 Dec. 2019), pp.1-11, 11 p.
Publisher
Hindawi Publishing Corporation
Publication Date
2019-04-17
Country of Publication
Egypt
No. of Pages
11
Main Subjects
Abstract EN
Indoxyl sulfate (IS) accumulation occurs early during chronic kidney disease (CKD) progression and contributes to renal dysfunction by inducing fibrosis, inflammation, oxidative stress, and tissue remodeling.
Renal toxicity of high IS concentrations (250 μM) has been widely explored, particularly in resident tubular and glomerular cells, while the effect of a moderate IS increase on kidneys is still mostly unknown.
To define the effects of IS accumulation on renal fibroblasts, we first analyzed kidneys of C57BL/6 mice receiving IS (0.1%) in drinking water for 12 weeks.
As a next step, we treated renal fibroblasts (NRK-49F) with IS (20 μM) with or without the HSP90 inhibitor 17-AAG (1 μM).
In mouse kidneys, IS increased the collagen deposition and HSP90 and α-SMA expression (immunohistochemistry) in interstitial fibroblasts and caused tubular necrosis (histological H&E and picrosirius red staining).
In NRK-49F cells, IS induced MCP1, TGF-β, collagen I, α-SMA, and HSP90 gene/protein expression and Smad2/3 pathway activation.
IS had no effects on fibroblast proliferation and ROS production.
17-AAG counteracted IS-induced MCP1, TGF-β, collagen I, and α-SMA expression and Smad2/3 phosphorylation.
Our study demonstrates that the IS increase promotes renal fibroblast activation by a HSP90-dependent pathway and indicates HSP90 inhibition as a potential strategy to restrain IS-induced kidney inflammation and fibrosis in CKD.
American Psychological Association (APA)
Milanesi, Samantha& Garibaldi, Silvano& Saio, Michela& Ghigliotti, Giorgio& Picciotto, Daniela& Ameri, Pietro…[et al.]. 2019. Indoxyl Sulfate Induces Renal Fibroblast Activation through a Targetable Heat Shock Protein 90-Dependent Pathway. Oxidative Medicine and Cellular Longevity،Vol. 2019, no. 2019, pp.1-11.
https://search.emarefa.net/detail/BIM-1202477
Modern Language Association (MLA)
Milanesi, Samantha…[et al.]. Indoxyl Sulfate Induces Renal Fibroblast Activation through a Targetable Heat Shock Protein 90-Dependent Pathway. Oxidative Medicine and Cellular Longevity No. 2019 (2019), pp.1-11.
https://search.emarefa.net/detail/BIM-1202477
American Medical Association (AMA)
Milanesi, Samantha& Garibaldi, Silvano& Saio, Michela& Ghigliotti, Giorgio& Picciotto, Daniela& Ameri, Pietro…[et al.]. Indoxyl Sulfate Induces Renal Fibroblast Activation through a Targetable Heat Shock Protein 90-Dependent Pathway. Oxidative Medicine and Cellular Longevity. 2019. Vol. 2019, no. 2019, pp.1-11.
https://search.emarefa.net/detail/BIM-1202477
Data Type
Journal Articles
Language
English
Notes
Includes bibliographical references
Record ID
BIM-1202477