Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2023 Mar;36(2):385-395.
doi: 10.1007/s40620-022-01551-2. Epub 2023 Jan 9.

Glomerular expression and urinary excretion of fatty acid-binding protein 4 in IgA nephropathy

Marenao Tanaka  1 , Norihito Moniwa  2 , Chieko Nogi  3 , Toshiki Kano  3 , Megumi Matsumoto  1 , Akiko Sakai  1 , Takuto Maeda  2 , Hideki Takizawa  2 , Yayoi Ogawa  4 , Katsuhiko Asanuma  5 , Yusuke Suzuki  3 , Masato Furuhashi  6
Affiliations

Glomerular expression and urinary excretion of fatty acid-binding protein 4 in IgA nephropathy

Marenao Tanaka et al. J Nephrol. 2023 Mar.

Abstract

Background: Fatty acid-binding protein 4 (FABP4) is secreted from adipocytes and macrophages in adipose tissue and acts as an adipokine. It has recently been reported that FABP4, but not liver-type FABP (L-FABP/FABP1), is also expressed in injured glomerular endothelial cells and infiltrating macrophages in the glomerulus and that urinary FABP4 (U-FABP4) is associated with proteinuria and kidney function impairment in nephrotic patients. However, the link between glomerular FABP4 and U-FABP4 has not been fully addressed in IgA nephropathy (IgAN).

Methods: We investigated the involvement of FABP4 in human and mouse IgAN.

Results: In patients with IgAN (n = 23), the ratio of FABP4-positive area to total area within glomeruli (G-FABP4-Area) and U-FABP4 were positively correlated with proteinuria and were negatively correlated with eGFR. In 4-28-week-old male grouped ddY mice, a spontaneous IgAN-prone mouse model, FABP4 was detected in glomerular endothelial cells and macrophages, and G-FABP4-Area was positively correlated with urinary albumin-to-creatinine ratio (r = 0.957, P < 0.001). Endoplasmic reticulum stress markers were detected in glomeruli of human and mouse IgAN. In human renal glomerular endothelial cells, FABP4 was induced by treatment with vascular endothelial growth factor and was secreted from the cells. Treatment of human renal glomerular endothelial cells or mouse podocytes with palmitate-bound recombinant FABP4 significantly increased gene expression of inflammatory cytokines and endoplasmic reticulum stress markers, and the effects of FABP4 in podocytes were attenuated in the presence of an anti-FABP4 antibody.

Conclusion: FABP4 in the glomerulus contributes to proteinuria in IgAN, and U-FABP4 level is a useful surrogate biomarker for glomerular damage in IgAN.

Keywords: Endoplasmic reticulum stress; Glomerular endothelial cells; IgA nephropathy; Inflammation; Podocytes.

PubMed Disclaimer

References

    1. Rodrigues JC, Haas M, Reich HN (2017) IgA nephropathy. Clin J Am Soc Nephrol 12:677–686 - PMC - PubMed
    1. Pattrapornpisut P, Avila-Casado C, Reich HN (2021) IgA nephropathy: core curriculum 2021. Am J Kidney Dis 78:429–441 - PubMed
    1. Koyama A, Igarashi M, Kobayashi M (1997) Natural history and risk factors for immunoglobulin A nephropathy in Japan. Research Group on Progressive Renal Diseases. Am J Kidney Dis 29:526–532 - PubMed
    1. Ruan XZ, Varghese Z, Moorhead JF (2009) An update on the lipid nephrotoxicity hypothesis. Nat Rev Nephrol 5:713–721 - PubMed
    1. Izquierdo-Lahuerta A, Martinez-Garcia C, Medina-Gomez G (2016) Lipotoxicity as a trigger factor of renal disease. J Nephrol 29:603–610 - PubMed

Publication types

Substances