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CC BY-NC-ND 4.0 · Exp Clin Endocrinol Diabetes 2024; 132(07): 396-406
DOI: 10.1055/a-2301-3970
Article

Protective Role of MerTK in Diabetic Peripheral Neuropathy via Inhibition of the NF-κB Signaling Pathway

Xiaoyang Su
1   Department of Critical Care Medicine, The First Affiliated Hospital of Kunming Medical University, Kunming 650032, Yunnan, China
,
Wenting Chen
2   Department of Endocrinology, The First Affiliated Hospital of Kunming Medical University, Kunming 650032, Yunnan, China
,
Yidan Fu
2   Department of Endocrinology, The First Affiliated Hospital of Kunming Medical University, Kunming 650032, Yunnan, China
,
Bian Wu
3   Department of General Surgery II, The First People’s Hospital of Yunnan Province, Yunnan Key Laboratory of Innovative Application of Traditional Chinese Medicine, Kunming 650032, Yunnan, China
,
Fugang Mao
4   Department of Ultrasound, The First People’s Hospital of Yunnan Province, The Affiliated Hospital of Kunming University of Science and Technology, Kunming 650032, Yunnan, China
,
Yan Zhao
2   Department of Endocrinology, The First Affiliated Hospital of Kunming Medical University, Kunming 650032, Yunnan, China
,
Qiuping Yang
2   Department of Endocrinology, The First Affiliated Hospital of Kunming Medical University, Kunming 650032, Yunnan, China
,
Danfeng Lan
5   Department of Gastroenterology, The First People’s Hospital of Yunnan Province, Yunnan Digestive Disease Clinical Medical Center, Kunming 650032, Yunnan, China
› Author Affiliations Fundings National Natural Science Foundation of China — http://dx.doi.org/10.13039/501100001809; 81860105 the Yunnan Key Laboratory of Innovative Application of Traditional Chinese Medicine — 202105AG070032 the Yunnan Health Training Project of High Level Talents — YNWR-QNBJ-2020–236 the Special Joint Program of Yunnan Province — 202001AY070001–159 This work was supported by the National Natural Science Foundation of China (81860105), the Special Joint Program of Yunnan Province (202001AY070001–159, 202401AY070001–040), the Yunnan Youth Top Talent Project of High-Level Talents (YNWR-QNBJ-2020–236), the Yunnan Health Training Project of High-Level Talents Medical Reserve Talent Project (H-2019036), the Kunming University of Science and Technology, the First People's Hospital of Yunnan Province Joint Special Project on Medical Research (KUST- KH2022013Y), and the Yunnan Key Laboratory of Innovative Application of Traditional Chinese Medicine (202105AG070032).
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Abstract

Introduction Diabetic peripheral neuropathy (DPN) impacts patient quality of life. In such patients, increased expression of mer tyrosine kinase (MerTK) has been demonstrated; however, its mechanism of action remains unclear. In this study, type 2 diabetes mellitus (T2DM) and DPN models were established in Sprague Dawley rats via low-dose streptozotocin and a high-fat diet and the mode of action of MerTK was examined.

Methods MerTK-specific inhibitors were administered by gavage once daily for 2 weeks. Sciatic nerve conduction velocity and nerve structure were measured. The levels of MerTK, nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1β), and relevant biochemical indexes were detected.

Results The study revealed upregulation of MerTK expression in T2DM and more so in DPN groups. Inhibiting MerTK led to reduced nerve conduction velocity and further deterioration of sciatic nerve structure, as evidenced by structural morphology. Concurrently, serum levels of total cholesterol, glycated hemoglobin, and triglyceride significantly increased. Moreover, levels of NF-κB increased in both serum and nerve tissue, alongside a significant rise in TNF-α and IL-1β expressions. MerTK could bind to the inhibitor of kappa B kinase beta (Ikbkb) in Schwann cells, establishing Ikbkb as a precursor to NF-κB activation.

Discussion Inhibition of MerTK exacerbates neuropathy, indicating its protective role in DPN by suppressing the NF-κB pathway, highlighting a potential new target for its diagnosis and treatment.

Keywords

diabetic peripheral neuropathy - MerTK - NF-κB signaling pathway - inflammatory factors - protective effect


Publication History

Received: 28 November 2023
Received: 21 March 2024

Accepted: 26 March 2024

Accepted Manuscript online:
08 April 2024

Article published online:
10 May 2024

© 2024. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial-License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/).

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