甲基乙二醛衍生的晚期糖基化终产物通过激活肾近端上皮细胞中的ERK/JNK/NF-κB途径诱导基质金属蛋白酶。
Methylglyoxal-derived advanced glycation end products induce matrix metalloproteinases through activation of ERK/JNK/NF-κB pathway in kidney proximal epithelial cells.
作者信息
Jeong So-Ra, Park Ho-Young, Kim Yoonsook, Lee Kwang-Won
机构信息
1Department of Biotechnology, College of Life Sciences and Biotechnology, Korea University, Anam-Dong, Sungbuk-Gu, Seoul, 02841 Republic of Korea.
2Division of Functional Food Research, Korea Food Research Institute, Wanju-gun, Jeollabuk-do 55365 Republic of Korea.
出版信息
Food Sci Biotechnol. 2019 Nov 28;29(5):675-682. doi: 10.1007/s10068-019-00704-7. eCollection 2020 May.
Abstract
The accumulation of reactive α-dicarbonyl leading to advanced glycation end products (AGEs) have been linked to pathophysiological diseases in many studies, such as atherosclerosis, cataract, cancer, and diabetic nephropathy. Glycation-generated AGEs increase the expression of inflammatory cytokines by transferring signals to the cell by binding them to the receptor for AGEs (RAGE) on their cell surface. The effect of methylglyoxal-derived AGEs (AGE-4) on the induction of matrix metalloproteinases (MMPs) in rat ordinary kidney cells (NRK-52E) was explored in this research, among other AGEs. The cell treated with 100 μg/mL AGE-4 for 24 h showed a substantial rise in MMP-2 and MMP-9 expression relative to BSA control only and other AGEs through ERK, JNK, and NF-B pathways. Our findings therefore suggest that AGE-4 expresses MMPs through the AGE-4-RAGE axis, activating MAPK signals that may contribute to dysfunction of the kidney cell.
摘要
在许多研究中，反应性α-二羰基化合物积累导致晚期糖基化终产物（AGEs）的形成，这与动脉粥样硬化、白内障、癌症和糖尿病肾病等病理生理疾病有关。糖基化产生的AGEs通过与细胞表面的AGE受体（RAGE）结合，将信号传递给细胞，从而增加炎症细胞因子的表达。本研究除了探究其他AGEs外，还探讨了甲基乙二醛衍生的AGEs（AGE-4）对大鼠正常肾细胞（NRK-52E）中基质金属蛋白酶（MMPs）诱导作用的影响。用100μg/mL AGE-4处理细胞24小时后，相对于仅用牛血清白蛋白（BSA）作为对照以及其他AGEs处理的细胞，通过细胞外调节蛋白激酶（ERK）、应激活化蛋白激酶（JNK）和核因子κB（NF-κB）途径，MMP-2和MMP-9的表达显著升高。因此，我们的研究结果表明，AGE-4通过AGE-4-RAGE轴表达MMPs，激活丝裂原活化蛋白激酶（MAPK）信号，这可能导致肾细胞功能障碍。
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