Ying Chen, Jun Tao, Yijun He, Xudong Hou, Ji Fang, Jiebo Huang, Li Wang, Junlong Shen, Bingbing Zhu, Niansong Wang, Aili Cao
{"title":"姜黄素在糖尿病肾病治疗中靶向 CXCL16 介导的荚膜细胞损伤和脂质蓄积。","authors":"Ying Chen, Jun Tao, Yijun He, Xudong Hou, Ji Fang, Jiebo Huang, Li Wang, Junlong Shen, Bingbing Zhu, Niansong Wang, Aili Cao","doi":"10.1007/s12272-024-01521-1","DOIUrl":null,"url":null,"abstract":"<div><p>Among the complications of diabetes, diabetic kidney disease (DKD) frequently emerges, typified by the detrimental effects on renal function, manifesting through inflammation, dysregulated lipid metabolism, and harm to podocytes. Existing research underscores the significance of the soluble form of C-X-C chemokine ligand 16 (CXCL16) within the context of renal impairments. However, whether CXCL16 is involved in the pathogenesis of DKD remains elusive. We report that CXCL16 levels in the serum and kidneys of individuals with DKD were elevated and correlated with various lipid parameters. The expression of CXCL16 in human podocytes subjected to high glucose or palmitic acid induction and exogenous CXCL16 administration in these cells were examined. Higher CXCL16 levels were linked to abnormal lipid metabolism. Exogenous CXCL16 administration induced lipid droplets, microfilament disorganization, apoptosis, oxidative stress, and inflammation, inhibited PPAR γ, up-regulated COX2 expression, and inhibited Nrf2 translocation in podocytes. Molecular analysis revealed that Curcumin (Cur), a polyphenolic compound derived from <i>Curcuma longa</i> and an Nrf2 agonist, targets the ATP-binding pocket of CXCL16, inhibiting its kinase activity. Meanwhile, Cur therapy alleviated podocyte injury, lipid accumulation, improved glomerulopathy, and reduced albuminuria. Furthermore, after silencing CXCL16 expression in podocytes using siRNA, the effects of exogenous CXCL16 were nullified, and Cur no longer exhibited any significant impact. Thus, CXCL16 participates in the pathogenesis of DKD. Inhibition of CXCL16 has shown promising results in experimental models, suggesting its beneficial effects in ameliorating DKD.</p></div>","PeriodicalId":8287,"journal":{"name":"Archives of Pharmacal Research","volume":"47 12","pages":"924 - 939"},"PeriodicalIF":6.9000,"publicationDate":"2024-11-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Curcumin targets CXCL16-mediated podocyte injury and lipid accumulation in diabetic kidney disease treatment\",\"authors\":\"Ying Chen, Jun Tao, Yijun He, Xudong Hou, Ji Fang, Jiebo Huang, Li Wang, Junlong Shen, Bingbing Zhu, Niansong Wang, Aili Cao\",\"doi\":\"10.1007/s12272-024-01521-1\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><p>Among the complications of diabetes, diabetic kidney disease (DKD) frequently emerges, typified by the detrimental effects on renal function, manifesting through inflammation, dysregulated lipid metabolism, and harm to podocytes. Existing research underscores the significance of the soluble form of C-X-C chemokine ligand 16 (CXCL16) within the context of renal impairments. However, whether CXCL16 is involved in the pathogenesis of DKD remains elusive. We report that CXCL16 levels in the serum and kidneys of individuals with DKD were elevated and correlated with various lipid parameters. The expression of CXCL16 in human podocytes subjected to high glucose or palmitic acid induction and exogenous CXCL16 administration in these cells were examined. Higher CXCL16 levels were linked to abnormal lipid metabolism. Exogenous CXCL16 administration induced lipid droplets, microfilament disorganization, apoptosis, oxidative stress, and inflammation, inhibited PPAR γ, up-regulated COX2 expression, and inhibited Nrf2 translocation in podocytes. Molecular analysis revealed that Curcumin (Cur), a polyphenolic compound derived from <i>Curcuma longa</i> and an Nrf2 agonist, targets the ATP-binding pocket of CXCL16, inhibiting its kinase activity. Meanwhile, Cur therapy alleviated podocyte injury, lipid accumulation, improved glomerulopathy, and reduced albuminuria. Furthermore, after silencing CXCL16 expression in podocytes using siRNA, the effects of exogenous CXCL16 were nullified, and Cur no longer exhibited any significant impact. Thus, CXCL16 participates in the pathogenesis of DKD. Inhibition of CXCL16 has shown promising results in experimental models, suggesting its beneficial effects in ameliorating DKD.</p></div>\",\"PeriodicalId\":8287,\"journal\":{\"name\":\"Archives of Pharmacal Research\",\"volume\":\"47 12\",\"pages\":\"924 - 939\"},\"PeriodicalIF\":6.9000,\"publicationDate\":\"2024-11-28\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Archives of Pharmacal Research\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://link.springer.com/article/10.1007/s12272-024-01521-1\",\"RegionNum\":3,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"CHEMISTRY, MEDICINAL\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Archives of Pharmacal Research","FirstCategoryId":"3","ListUrlMain":"https://link.springer.com/article/10.1007/s12272-024-01521-1","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CHEMISTRY, MEDICINAL","Score":null,"Total":0}
Curcumin targets CXCL16-mediated podocyte injury and lipid accumulation in diabetic kidney disease treatment
Among the complications of diabetes, diabetic kidney disease (DKD) frequently emerges, typified by the detrimental effects on renal function, manifesting through inflammation, dysregulated lipid metabolism, and harm to podocytes. Existing research underscores the significance of the soluble form of C-X-C chemokine ligand 16 (CXCL16) within the context of renal impairments. However, whether CXCL16 is involved in the pathogenesis of DKD remains elusive. We report that CXCL16 levels in the serum and kidneys of individuals with DKD were elevated and correlated with various lipid parameters. The expression of CXCL16 in human podocytes subjected to high glucose or palmitic acid induction and exogenous CXCL16 administration in these cells were examined. Higher CXCL16 levels were linked to abnormal lipid metabolism. Exogenous CXCL16 administration induced lipid droplets, microfilament disorganization, apoptosis, oxidative stress, and inflammation, inhibited PPAR γ, up-regulated COX2 expression, and inhibited Nrf2 translocation in podocytes. Molecular analysis revealed that Curcumin (Cur), a polyphenolic compound derived from Curcuma longa and an Nrf2 agonist, targets the ATP-binding pocket of CXCL16, inhibiting its kinase activity. Meanwhile, Cur therapy alleviated podocyte injury, lipid accumulation, improved glomerulopathy, and reduced albuminuria. Furthermore, after silencing CXCL16 expression in podocytes using siRNA, the effects of exogenous CXCL16 were nullified, and Cur no longer exhibited any significant impact. Thus, CXCL16 participates in the pathogenesis of DKD. Inhibition of CXCL16 has shown promising results in experimental models, suggesting its beneficial effects in ameliorating DKD.
期刊介绍:
Archives of Pharmacal Research is the official journal of the Pharmaceutical Society of Korea and has been published since 1976. Archives of Pharmacal Research is an interdisciplinary journal devoted to the publication of original scientific research papers and reviews in the fields of drug discovery, drug development, and drug actions with a view to providing fundamental and novel information on drugs and drug candidates.