Department of Neurosurgery, All India Institute of Medical Sciences (AIIMS), New Delhi, India; Centre of Excellence for Epilepsy: A Joint Collaboration of NBRC and AIIMS, New Delhi, India.
Department of Neurosurgery, All India Institute of Medical Sciences (AIIMS), New Delhi, India; Dr. B.R. Ambedkar Center for Biomedical Research, University of Delhi, New Delhi, India.
Epilepsy Res. 2018 Oct;146:144-150. doi: 10.1016/j.eplepsyres.2018.08.004. Epub 2018 Aug 20.
Transforming growth factor beta (TGFβ) signalling cascade has been implicated in enhancing neuronal excitability and excitatory synaptogenesis following blood brain barrier (BBB) damage and inflammation. We aimed to study if TGFβ signalling expression is altered in patients with Hippocampal Sclerosis (HS). We probed into the protein expression level of the ligand transforming growth factor beta 1 (TGFβ1), transforming growth factor beta receptor II (TGFβRII) and downstream signalling molecule SMAD3 and phosphorylated SMAD3 (pSMAD3) on surgically resected hippocampal samples of thirty-four patients with HS through immuno-blotting. The increase in protein expression level of the ligand TGFβ1 was 285 ± 1.15% higher and its receptor TGFβRII was 170 ± 0.98% higher in hippocampus of patients with HS in comparison to the autopsy hippocampal control samples. The expression of the downstream signalling molecules, SMAD3 is 157 ± 0.13% and 106 ± 0.17% higher in patients with HS as compared to both types of non-seizure controls. The expression of active form of SMAD3, pSMAD3 (2.6010 ± 1.2735) was significantly upregulated in hippocampus of patients with HS compared to autopsy hippocampal controls (0.7899 ± 0.3688). While the expression of pSMAD3 (1.527 ± 0.9425) was significantly upregulated in hippocampus of patients with HS with another type of non-seizure control viz. tumour periphery tissue (0.5791 ± 0.2679), hence strongly supporting the altered expression of the pathway. This study provides the first evidence of alteration of TGFβ pathway in patients with HS which could be a potential therapeutic target.
转化生长因子β（TGFβ）信号级联在血脑屏障（BBB）损伤和炎症后增强神经元兴奋性和兴奋性突触发生中起作用。我们旨在研究 Hippocampal Sclerosis（HS）患者中 TGFβ 信号表达是否改变。我们通过免疫印迹法探查了 34 例 HS 患者手术切除的海马样本中配体转化生长因子β 1（TGFβ1）、转化生长因子β受体 II（TGFβRII）和下游信号分子 SMAD3 及磷酸化 SMAD3（pSMAD3）的蛋白表达水平。与尸检海马对照样本相比，HS 患者海马中配体 TGFβ1 的蛋白表达水平增加了 285±1.15%，其受体 TGFβRII 增加了 170±0.98%。下游信号分子 SMAD3 的表达在 HS 患者中分别增加了 157±0.13%和 106±0.17%，与两种非癫痫对照相比。与尸检海马对照相比（0.7899±0.3688），HS 患者海马中活性形式的 SMAD3，pSMAD3（2.6010±1.2735）的表达明显上调。而 HS 患者海马中 pSMAD3（1.527±0.9425）的表达与另一种非癫痫对照（肿瘤周边组织）相比明显上调（0.5791±0.2679），这强烈支持该途径的改变表达。本研究首次提供了 HS 患者 TGFβ 途径改变的证据，这可能是一个潜在的治疗靶点。
