Short salsalate administration affects cell proliferation, metabolism, and inflammation in polycystic kidney disease Article Swipe

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Anish A. Kanhai , Elena Sánchez‐López , Thomas B. Kuipers , Jan B. van Klinken , Kyra L. Dijkstra , Inge van der Veen , Hans J. Baelde , Xuewen Song , York Pei , Hailiang Mei , Wouter N. Leonhard , Oleg A. Mayboroda , Dorien J.M. Peters ·

YOU? · · 2023 · Open Access · · DOI: https://doi.org/10.1016/j.isci.2023.108278

Metabolic reprogramming is a driver of autosomal dominant polycystic kidney disease (ADPKD) progression and a potential therapeutic intervention route. We showed before that the AMP-associated protein kinase (AMPK) activator salsalate attenuates cystic disease progression. Here, we aim to study the early, direct effects of short salsalate treatment in adult-onset conditional Pkd1 deletion mice. Cystic mice were treated with salsalate for two weeks, after which NMR metabolomics and RNA sequencing analyses were performed. Pkd1 deletion resulted in clear metabolomic dysregulation. Short salsalate treatment has small, but significant, effects, reverting acetylcarnitine and phosphocholine concentrations back to wildtype levels, and showing associations with altered purine metabolism. RNA sequencing revealed that short salsalate treatment, next to restoring energy metabolism toward wildtype levels, also affects cell proliferation and inflammation, in PKD. We show that salsalate positively affects major dysregulated processes in ADPKD: energy metabolism, cell proliferation, and inflammation, providing more insights into its working mechanisms.

Related Topics

Polycystic Kidney Disease

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Autosomal dominant polycystic kidney disease Internal medicine Inflammation Endocrinology AMPK PKD1 Medicine Polycystic kidney disease Biology Disease Kinase Protein kinase A Biochemistry

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Type: article
Language: en
Landing Page: https://doi.org/10.1016/j.isci.2023.108278
PDF: https://doi.org/10.1016/j.isci.2023.108278
OA Status: gold
Cited By: 1
References: 100
Related Works: 10
OpenAlex ID: https://openalex.org/W4387766319

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DOI: https://doi.org/10.1016/j.isci.2023.108278

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Title: Short salsalate administration affects cell proliferation, metabolism, and inflammation in polycystic kidney disease

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Language: en

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Publication year: 2023

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Publication date: 2023-10-19

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Authors: Anish A. Kanhai, Elena Sánchez‐López, Thomas B. Kuipers, Jan B. van Klinken, Kyra L. Dijkstra, Inge van der Veen, Hans J. Baelde, Xuewen Song, York Pei, Hailiang Mei, Wouter N. Leonhard, Oleg A. Mayboroda, Dorien J.M. Peters

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Landing page: https://doi.org/10.1016/j.isci.2023.108278

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Concepts: Autosomal dominant polycystic kidney disease, Internal medicine, Inflammation, Endocrinology, AMPK, PKD1, Medicine, Polycystic kidney disease, Biology, Disease, Kinase, Protein kinase A, Biochemistry

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Cited by: 1

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