Fatty acid-binding protein 4 downregulation drives calcification in the development of kidney stone disease - PubMed (original) (raw)

. 2020 May;97(5):1042-1056.

doi: 10.1016/j.kint.2020.01.042. Epub 2020 Feb 29.

Ling Chen 2, Manint Usawachintachit 3, Shuzo Hamamoto 4, Misun Kang 2, Teruaki Sugino 4, Rei Unno 4, David T Tzou 5, Benjamin A Sherer 5, Atsushi Okada 4, Takahiro Yasui 4, Sunita P Ho 2, Marshall L Stoller 5, Thomas Chi 6

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Fatty acid-binding protein 4 downregulation drives calcification in the development of kidney stone disease

Kazumi Taguchi et al. Kidney Int. 2020 May.

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Abstract

Nephrolithiasis is a significant source of morbidity, and its incidence has increased significantly over the last decades. This rise has been attributed to concurrent increasing rates of obesity, associated with a 3-time risk of developing NL. To date, the mechanism by which obesity is linked to stone formation has not been elucidated. We aimed to utilize a transcriptomics approach to discover the missing link between these two epidemic diseases. We investigated gene expression profiling of nephrolithiasis patients by two RNA-sequencing approaches: comparison between renal papilla tissue with and without the presence of calcified Randall's plaques (RP), and comparison between the papilla, medulla, and cortex regions from within a single recurrent stone forming kidney. Results were overlaid between differently expressed genes found in the patient cohort and in the severely lithogenic kidney to identify common genes. Overlay of these two RNA-sequencing datasets demonstrated there is impairment of lipid metabolism in renal papilla tissue containing RP linked to downregulation of fatty acid binding protein (FABP) 4. Immunohistochemistry of human kidney specimens and microarray analysis of renal tissue from a nephrolithiasis mouse model confirmed that FABP4 downregulation is associated with renal stone formation. In a FABP4 knockout mouse model, FABP4 deficiency resulted in development of both renal and urinary crystals. Our study revealed that FABP4 plays an important, previously unrecognized role in kidney stone formation, providing a feasible mechanism to explain the link between nephrolithiasis and metabolic syndrome.

Keywords: RNA-sequence; Randall’s plaque; fatty acid–binding protein; kidney stone; metabolic syndrome.

Copyright © 2020 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.

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