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Epsin1-mediated exosomal sorting of Dll4 modulates the tubular-macrophage crosstalk in diabetic nephropathy.
Liu, Jia-Lu; Zhang, Lei; Huang, Ying; Li, Xiao-Hui; Liu, Yi-Fei; Zhang, Shu-Min; Zhao, Yue-E; Chen, Xiao-Jun; Liu, Yu; He, Li-Yu; Dong, Zheng; Liu, Fu-You; Sun, Lin; Xiao, Li.
Afiliação
  • Liu JL; Department of Nephrology, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China.
  • Zhang L; Department of Nephrology, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China.
  • Huang Y; Department of Nephrology, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China.
  • Li XH; Department of Nephrology, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China.
  • Liu YF; Department of Nephrology, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China.
  • Zhang SM; Department of Nephrology, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China.
  • Zhao YE; Department of Nephrology, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China.
  • Chen XJ; Department of Nephrology, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China.
  • Liu Y; Department of Nephrology, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China.
  • He LY; Department of Nephrology, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China.
  • Dong Z; Department of Nephrology, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China; Department of Cellular Biology and Anatomy, Medical College of Georgia at Augusta University, Augusta, GA, USA; Charlie Norwood VA Medical Center, Augusta, GA, USA.
  • Liu FY; Department of Nephrology, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China.
  • Sun L; Department of Nephrology, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China.
  • Xiao L; Department of Nephrology, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China. Electronic address: xiaolizndx@csu.edu.cn.
Mol Ther ; 31(5): 1451-1467, 2023 05 03.
Article em En | MEDLINE | ID: mdl-37016580
ABSTRACT
Tubular epithelial cells (TECs) play critical roles in the development of diabetic nephropathy (DN), and can activate macrophages through the secretion of exosomes. However, the mechanism(s) of TEC-exosomes in macrophage activation under DN remains unknown. By mass spectrometry, 1,644 differentially expressed proteins, especially Dll4, were detected in the urine exosomes of DN patients compared with controls, which was confirmed by western blot assay. Elevated Epsin1 and Dll4/N1ICD expression was observed in kidney tissues in both DN patients and db/db mice and was positively associated with tubulointerstitial damage. Exosomes from high glucose (HG)-treated tubular cells (HK-2) with Epsin1 knockdown (KD) ameliorated macrophage activation, TNF-α, and IL-6 expression, and tubulointerstitial damage in C57BL/6 mice in vivo. In an in vitro study, enriched Dll4 was confirmed in HK-2 cells stimulated with HG, which was captured by THP-1 cells and promoted M1 macrophage activation. In addition, Epsin1 modulated the content of Dll4 in TEC-exosomes stimulated with HG. TEC-exosomes with Epsin1-KD significantly inhibited N1ICD activation and iNOS expression in THP-1 cells compared with incubation with HG alone. These findings suggested that Epsin1 could modulate tubular-macrophage crosstalk in DN by mediating exosomal sorting of Dll4 and Notch1 activation.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Diabetes Mellitus / Nefropatias Diabéticas Limite: Animals Idioma: En Revista: Mol Ther Ano de publicação: 2023 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Diabetes Mellitus / Nefropatias Diabéticas Limite: Animals Idioma: En Revista: Mol Ther Ano de publicação: 2023 Tipo de documento: Article