Thymosin β4 promotes the recovery of peripheral neuropathy in type II diabetic mice

NEUROBIOLOGY OF DISEASE

卷:48

Article

Wang, Lei¹  Chopp, Michael^1,2  Szalad, Alexandra¹  Liu, Zhongwu¹  Lu, Mei¹  Zhang, Li¹  Zhang, Jing¹  Zhang, Rui Lan¹  Morris, Dan¹  Zhang, Zheng Gang¹ 

[1] Henry Ford Hosp, Dept Neurol, Detroit, MI 48202 USA

[2] Oakland Univ, Dept Phys, Rochester, MI 48309 USA

关键词: T beta 4;    Peripheral neuropathy;    Diabetes;    Mice;   

DOI  :  10.1016/j.nbd.2012.08.002

来源: Elsevier

【 摘 要 】

Peripheral neuropathy is one of the most common complications of diabetes mellitus. Using a mouse model of diabetic peripheral neuropathy, we tested the hypothesis that thymosin beta 4 (T beta 4) ameliorates diabetes-induced neurovascular dysfunction in the sciatic nerve and promotes recovery of neurological function from diabetic peripheral neuropathy. T beta 4 treatment of diabetic mice increased functional vascular density and regional blood flow in the sciatic nerve, and improved nerve function. T beta 4 upregulated angiopoietin-1 (Ang1) expression, but suppressed Ang2 expression in endothelial and Schwann cells in the diabetic sciatic nerve. In vitro, incubation of Human Umbilical Vein Endothelial Cells (HUVECs) with T beta 4 under high glucose condition completely abolished high glucose-downregulated Ang1 expression and high glucose-reduced capillary-like tube formation. Moreover, incubation of HUVECs under high glucose with conditioned medium collected from Human Schwann Cells (HSCs) treated with T beta 4 significantly reversed high glucose-decreased capillary-like tube formation. PI3K/Akt signaling pathway is involved in T beta 4-regulated Ang1 expression on endothelial and Schwann cells. These data indicate that T beta 4 likely acts on endothelial cells and Schwann cells to preserve and/or restore vascular function in the sciatic nerve which facilitates improvement of peripheral nerve function under diabetic neuropathy. Thus, T beta 4 has potential for the treatment of diabetic peripheral neuropathy. (c) 2012 Elsevier Inc. All rights reserved.

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