![]() ![]() ![]() The continuous stimulation of risk factors usually causes damage to HK-2 cells in renal tubular epithelial cells, including high glucose levels, proteinuria, and age-modifying proteins that all lead to extracellular matrix (ECM) deposition and abnormal synthesis and degradation of epithelial proteins, leading to epithelial-mesenchymal transition (EMT) and even interstitial fibrosis ( 14– 17). In addition, AGEs are the main cause of diabetic microvascular disease ( 13). AGEs cause oxidative stress, trigger excessive reactive oxygen species, promote the production and release of inflammatory cytokines, and aggravate the development of diabetes, chronic renal failure, cardiovascular diseases, and neurological diseases ( 9– 12). It is also the most common and serious chronic complication of type 2 diabetes mellitus (T2DM), which often leads to end-stage renal failure in patients with diabetes ( 5, 6).Īdvanced glycation end products (AGEs) are the end products of non-enzymatic glycation reaction (Maillard reaction), which refer to the heterogeneous molecules formed by the reaction of proteins, lipids, or nucleic acids with glucose or other reducing monosaccharides without the participation of enzymes ( 7, 8). Diabetic kidney disease (DKD), known as diabetic glomerulosclerosis, is one of the most common microvascular complications of diabetes mellitus (DM) ( 3, 4). Taken together, JMJD1A/NR4A1 signaling can regulate the procession of renal tubular epithelial interstitial fibrosis induced by AGEs in HK-2.ĭiabetes is a metabolic disease characterized by hyperglycemia, mainly divided into type 1 diabetes, type 2 diabetes, gestational diabetes, and special type diabetes ( 1, 2). Meanwhile, NR4A1 inhibitor can promote the expression of fibrosis-related factors such as VIM, a-SMA in HK-2 cells, and aggravate the process of fibrosis. Further analysis showed that JMJD1A overexpression could accelerate the progression of AGEs-induced renal fibrosis by reducing the expression of NR4A1 in HK-2 cells. In order to determine the downstream pathway, we screened out JMJD1A downstream transcription factors by RNA-seq. This is consistent with the results of our in vitro experiments. At the same time, in the DKD animal model induced by unilateral nephrectomy plus streptozotocin (STZ), IHC immunohistochemical staining showed that compared with the control group, the expressions of JMJD1A, FN, and COL1 in the model group were all increased, masson staining results also show that the model group has typical fibrotic changes. The results showed that AGEs could upregulate JMJD1A, and the expressions of related fibrotic factor were also increased. The molecular mechanism study was performed in AGEs-induced HK-2 cells by gene expression analysis, RNA sequencing (RNA-seq), and JMJD1A lentiviral knockdown and overexpression particle transfection. In this work, we investigated the functional role of JMJD1A involved in DKD progression. However, the underlying epigenetic mechanisms remain to be further investigated. Advanced glycation end products (AGEs) induce epithelial-mesenchymal transformation (EMT) of renal tubular epithelial cells (HK-2), resulting in renal tubulointerstitial fibrosis. 3The Affiliated Jiangmen Traditional Chinese Medicine Hospital, Jinan University, Guangzhou, Chinaĭiabetic kidney disease (DKD) is one of the most serious complications of diabetic patients.2Zhujiang Hospital, Southern Medical University, Guangzhou, China. ![]() 1School of Traditional Chinese Medicine, Southern Medical University, Guangzhou, China.Shaoting Wang 1 † Anna Zuo 1 † Weiqiang Jiang 2 † Jiarun Xie 1 Haoyu Lin 1 Wei Sun 1 Min Zhao 2 Jinjin Xia 2 Junqiao Shao 1 Xiaoshan Zhao 1 Donghui Liang 1,2 Aicheng Yang 3 * Jia Sun 2 * Ming Wang 1,2 * ![]()
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