Painful Diabetic Neuropathy Is Associated with Compromised Microglial IGF-1 Signaling Which Can Be Rescued by Green Tea Polyphenol EGCG in Mice.
Painful Diabetic Neuropathy Is Associated with Compromised Microglial IGF-1 Signaling Which Can Be Rescued by Green Tea Polyphenol EGCG in Mice.
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疼痛性糖尿病神经病变与小胶质细胞 IGF-1 信号传导受损有关，而绿茶多酚 EGCG 可以在小鼠体内挽救这种信号传导
DOI：
10.1155/2022/6773662
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发表时间：
2022
影响因子：
--
通讯作者：
Wang HB
中科院分区：
文献类型：
--
作者：
Chen X;Le Y;Tang SQ;He WY;He J;Wang YH;Wang HB
糖尿病痛性神经病变（PDN）是糖尿病常见且棘手的并发症，目前尚无有效的治疗方法。PDN的特征在于特定的脊髓小胶质细胞介导的神经炎症。胰岛素样生长因子1（IGF-1）主要来源于大脑中的小胶质细胞，并在避免小胶质细胞转化为促炎性M1表型方面发挥重要作用。鉴于表没食子儿茶素-3-没食子酸酯（EGCG）是一种有效的抗炎剂，可以调节IGF-1信号传导，我们推测，EGCG给药可能会减少脊髓小胶质细胞相关的神经炎症，并通过IGF-1/IGF 1 R信号传导对抗PDN的发展。 通过单次腹膜内（i. p.）小鼠注射链脲佐菌素（STZ）。Western blot和免疫荧光法检测IGF-1及其受体IGF 1 R、白细胞介素1β（IL-1β）、肿瘤坏死因子α（TNF-α）和诱导型一氧化氮合酶（iNOS）的蛋白表达水平。 脊髓IGF-1表达沿着糖尿病小鼠疼痛样行为、脊髓神经炎症（IL-1β、TNF-α和Iba-1+小胶质细胞增加）和M1小胶质细胞极化（iNOS+Iba-1+小胶质细胞增加）。IGF-1可与神经元、星形胶质细胞和小胶质细胞共定位，但在T1 DM小鼠中仅小胶质细胞IGF-1被抑制。此外，我们发现，给予小鼠重组IGF-1（rIGF-1）以及i.t.腹腔注射或腹腔注射EGCG可减轻糖尿病引起的痛样行为，减少神经炎症（抑制IL-1β、TNF-α和Iba-1+小胶质细胞），阻止M1小胶质细胞极化（减少iNOS+Iba-1+小胶质细胞），恢复小胶质细胞IGF-1表达。 我们的数据强调了维持脊髓IGF-1信号在治疗PDN中小胶质细胞相关神经炎症中的重要性。这项研究还提供了新的见解EGCG对神经性疼痛和神经炎症通过IGF-1信号传导的神经保护机制，表明这种药物可能是一种有前途的治疗PDN在临床上。
Painful diabetic neuropathy (PDN) is a frequent and troublesome complication of diabetes, with little effective treatment. PDN is characterized by specific spinal microglia-mediated neuroinflammation. Insulin-like growth factor 1 (IGF-1) primarily derives from microglia in the brain and serves a vital role in averting the microglial transition into the proinflammatory M1 phenotype. Given that epigallocatechin-3-gallate (EGCG) is a potent anti-inflammatory agent that can regulate IGF-1 signaling, we speculated that EGCG administration might reduce spinal microglia-related neuroinflammation and combat the development of PDN through IGF-1/IGF1R signaling. Type 1 diabetes mellitus (T1DM) was established by a single intraperitoneal (i.p.) injection of streptozotocin (STZ) in mice. The protein expression level of IGF-1, its receptor IGF1R, interleukin 1β (IL-1β), tumor necrosis factor-α (TNF-α), and inducible nitric oxide synthase (iNOS) was determined by Western blot or immunofluorescence. The spinal IGF-1 expression markedly decreased along with the presence of pain-like behaviors, the spinal genesis of neuroinflammation (increased IL-1β, TNF-α, and Iba-1+ microglia), and the intensified M1 microglia polarization (increased iNOS+Iba-1+ microglia) in diabetic mice. IGF-1 could colocalize with neurons, astrocytes, and microglia, but only microglial IGF-1 was repressed in T1DM mice. Furthermore, we found that i.t. administration of mouse recombinant IGF-1 (rIGF-1) as well as i.t. or i.p. treatment with EGCG alleviated the diabetes-induced pain-like behaviors, reduced neuroinflammation (suppressed IL-1β, TNF-α, and Iba-1+ microglia), prevented the M1 microglia polarization (less iNOS+Iba-1+ microglia), and restored the microglial IGF-1 expression. Our data highlighted the importance of maintaining spinal IGF-1 signaling in treating microglia-related neuroinflammation in PDN. This study also provides novel insights into the neuroprotective mechanisms of EGCG against neuropathic pain and neuroinflammation through IGF-1 signaling, indicating that this agent may be a promising treatment for PDN in the clinical setting.
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影响因子：
7.7
作者：
Löken LS;Braz JM;Etlin A;Sadeghi M;Bernstein M;Jewell M;Steyert M;Kuhn J;Hamel K;Llewellyn-Smith IJ;Basbaum A
通讯作者：
Basbaum A
糖尿病的医疗标准 - 2010年。
影响因子：
16.2
作者：
American Diabetes Association
通讯作者：
American Diabetes Association
影响因子：
8.8
作者：
Jung, Y D;Kim, M S;Shin, B A;Chay, K O;Ahn, B W;Liu, W;Bucana, C D;Gallick, G E;Ellis, L M
通讯作者：
Ellis, L M
影响因子：
81.5
作者：
Feldman, Eva L.;Callaghan, Brian C.;Viswanathan, Vijay
通讯作者：
Viswanathan, Vijay
影响因子：
2.9
作者：
Bitar, MS;AlBustan, M;Pilcher, CWT
通讯作者：
Pilcher, CWT