Acidic fibroblast growth factor attenuates type 2 diabetes-induced demyelination via suppressing oxidative stress damage

Abstract

Prolonged type 2 diabetes mellitus (T2DM) produces a common complication, peripheral neuropathy, which is accompanied by nerve fiber disorder, axon atrophy, and demyelination. Growing evidence has characterized the beneficial effects of acidic fibroblast growth factor (aFGF) and shown that it relieves hyperglycemia, increases insulin sensitivity, and ameliorates neuropathic impairment. However, there is scarce evidence on the role of aFGF on remodeling of aberrant myelin under hyperglycemia condition. Presently, we observed that the expression of aFGF was rapidly decreased in a db/db T2DM mouse model. Administration of exogenous aFGF was sufficient to block acute demyelination and nerve fiber disorganization. Furthermore, this strong anti-demyelinating effect was most likely dominated by an aFGF-mediated increase of Schwann cell (SC) proliferation and migration as well as suppression of its apoptosis. Mechanistically, the beneficial biological effects of aFGF on SC behavior and abnormal myelin morphology were likely due to the inhibition of hyperglycemia-induced oxidative stress activation, which was most likely activated by kelch-like ECH-associated protein 1 (Keap1)/nuclear factor erythroid-derived-like 2 (Nrf2) signaling. Thus, this evidence indicates that aFGF is a promising protective agent for relieving myelin pathology through countering oxidative stress signaling cascades under diabetic conditions.

Antidiabetic Function of Lactobacillus fermentum MF423-Fermented Rice Bran and Its Effect on Gut Microbiota Structure in Type 2 Diabetic Mice

“…The development of insulin resistance affects oxidative stress in diabetic mice, leading to a significant increase in the levels of reactive oxygen species (ROS) and MDA in mice ( Li et al, 2021 ). Previous studies have proven that a large number of antioxidant enzymes in organisms, such as SOD, T-AOC and GSH-PX, can suppress oxidative stress by scavenging ROS levels ( Liu S. W. et al, 2020 ; Wu et al, 2021 ).…”

Advances in the Relationship Between Pyroptosis and Diabetic Neuropathy

“…However, it is still need to further explore the potential target of pyroptosis in DPN treatment. Our study found that fibroblast growth factor 1 (FGF1) expression is significantly inhibited after DPN, and exogenous FGF1 could alleviate DPN by alleviating oxidative stress in SCs (Li et al, 2021). Moreover, FGF21 and FGF10 also show significant therapeutic potential in peripheral nerve injury, both of which can reduce oxidative stress and promote neurological recovery.…”

Reduction in post-spinal cord injury spasticity by combination of peripheral nerve grafting and acidic fibroblast growth factor infusion in monkeys

“…38 Growing evidence has also shown that aFGF can ameliorate hyperglycemia, increase insulin sensitivity, and relieve neuropathic impairment. 39 The existing imaging methods have limited effectiveness for evaluating acute SCI during transient axonal dysfunction and spinal shock. However, neuroelectrophysiological techniques show high sensitivity and accuracy and can allow quantitative measurement of the degree of SCI and clarify the characteristics of SCI-induced functional loss.…”

“… 38 Growing evidence has also shown that aFGF can ameliorate hyperglycemia, increase insulin sensitivity, and relieve neuropathic impairment. 39 …”