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Review
. 2020 May 1;28(3):213-221.
doi: 10.4062/biomolther.2019.214.

Fyn Kinase: A Potential Therapeutic Target in Acute Kidney Injury

Md Jamal Uddin  1 , Debra Dorotea  1 , Eun Seon Pak  1 , Hunjoo Ha  1
Affiliations
Review

Fyn Kinase: A Potential Therapeutic Target in Acute Kidney Injury

Md Jamal Uddin et al. Biomol Ther (Seoul). .

Abstract

Acute kidney injury (AKI) is a common disease with a complex pathophysiology which significantly contributes to the development of chronic kidney disease and end stage kidney failure. Preventing AKI can consequently reduce mortality, morbidity, and healthcare burden. However, there are no effective drugs in use for either prevention or treatment of AKI. Developing therapeutic agents with pleiotropic effects covering multiple pathophysiological pathways are likely to be more effective in attenuating AKI. Fyn, a nonreceptor tyrosine kinase, has been acknowledged to integrate multiple injurious stimuli in the kidney. Limited studies have shown increased Fyn transcription level and activation under experimental AKI. Activated Fyn kinase propagates various downstream signaling pathways associated to the progression of AKI, such as oxidative stress, inflammation, endoplasmic reticulum stress, as well as autophagy dysfunction. The versatility of Fyn kinase in mediating various pathophysiological pathways suggests that its inhibition can be a potential strategy in attenuating AKI.

Keywords: Acute kidney injury; Autophagy; ER stress; Fyn kinase; Inflammation; Oxidative stress.

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Conflict of interest statement

CONFLICT OF INTEREST

All the authors declared no competing interests.

Figures

Fig. 1
Fig. 1
Src family kinase members and (B) their activation domain structure.
Fig. 2
Fig. 2
Fyn is increased in AKI. (A, B) AKI was induced by LPS (15 mg/kg, i.p). (A) Paraffin-embedded kidney sections were subjected to immunofluorescence staining using an anti-pFyn antibody (1:100; Santa Cruz Biotechnology, Inc., Santa Cruz, CA, USA) and anti-rabbit Alexa Fluor 588 (1:1,000; A11036; Life Technologies, Carlsbad, CA, USA). Nuclei were stained with DAPI. Images were taken using a Zeiss ApoTome Axiovert 200 M microscope (Carl Zeiss Microscopy GmbH, Jena, Germany). Scale bar indicates 50 μm. (B) pFyn and Fyn protein expression was detected by western blotting. Representative images are shown. (C) Transcription level of Fyn gene in IRI-induced AKI mice were analyzed using GEO database. Upper panel GSE52004; control (n=2), AKI (n=4) and lower panel GSE140988; control (n=3), AKI (n=3). NS, no sample.
Fig. 3
Fig. 3
Fyn signaling pathway. Activation of NOX, TLR, CD36, and TNFR may increase Fyn with or without ROS-mediated oxidative stress. Activated Fyn may i) suppress LKB1-AMPK and thus increases mTORC1-ER stress pathway and ii) activate STAT3 signaling which inhibits macroautophagy through suppression of VSP34, activates inflammation signaling, and mediates fibrosis. Additionally, Fyn also activates inflammation signaling (PKCδ>MAPK>NF-κB). All of these ultimately may contribute to kidney dysfunction. TNFR, tumor necrosis factor receptor.
Fig. 4
Fig. 4
Schematic diagram of Fyn involvement in AKI. Stress stimuli increases Fyn activation leading to ER stress, inflammation, and cell death. These events ultimately lead the cells to die, and AKI is started to develop. Using pharmacological or genetic approach to inhibit Fyn may attenuate Fyn-mediated AKI.
See this image and copyright information in PMC

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