Department of Experimental Surgery, Tangdu Hospital, The Fourth Military Medical University, Xi\'an, 710038, Shanxi, China.
Department of Experimental Surgery, Tangdu Hospital, Air Force Medical University, Xi\'an, 710038, China.
Front Biosci (Landmark Ed). 2019 Jan 1;24(3):482-493. doi: 10.2741/4730.
Transforming growth factor beta (TGF-beta) and Chloride channel-3 (CLC-3) are critical for inflammatory response, cellular proliferation and apoptosis in hippocampus neurons. However, the relationship between CLC-3 and TGF-beta/TGF-beta Receptor II (RII) pathway in diabetic encephalopathy (DE) is unknown. In this study, both diabetes rat model and diabetes cell model were employed to elucidate the mechanisms involved. The increased expressions of CLC-3 and TGF- beta RII with cognitive impairment were observed in diabetic rats. The most obvious reduction on the survival of HT22 cells was at 10 ng/ml or 15 ng/ml TGF- beta stimulation, while the expressions of CLC-3 and TGF-beta RII were significantly increased under high glucose condition. Moreover, the study showed that CLC-3 antagonists had no apparent effect on up-regulated TGF- beta RII, but TGF- beta 1 inhibitors could reduce the up-regulated CLC-3 under high glucose. Results from the present study indicated that CLC-3 and TGF- beta signals might be related to cognitive disorders. The CLC-3 might be modulated by TGF- beta /TGF- beta RII signaling pathway during the development of DE.
转化生长因子β（TGF-β）和氯离子通道-3（CLC-3）对于海马神经元中的炎症反应、细胞增殖和细胞凋亡至关重要。然而，糖尿病脑病（DE）中 CLC-3 和 TGF-β/TGF-β 受体 II（RII）通路之间的关系尚不清楚。在这项研究中，使用了糖尿病大鼠模型和糖尿病细胞模型来阐明相关机制。在糖尿病大鼠中观察到 CLC-3 和 TGF-β RII 的表达增加与认知障碍有关。在高糖条件下，HT22 细胞的存活率明显下降，在 10ng/ml 或 15ng/ml TGF-β刺激下最为明显，而 CLC-3 和 TGF-β RII 的表达显著增加。此外，研究表明，CLC-3 拮抗剂对 TGF-β RII 的上调没有明显影响，但 TGF-β1 抑制剂可降低高糖下上调的 CLC-3。本研究结果表明，CLC-3 和 TGF-β 信号可能与认知障碍有关。在 DE 的发展过程中，CLC-3 可能通过 TGF-β/TGF-β RII 信号通路进行调节。
