Curcumin Blunts IL-6 Dependent Endothelial‐to‐Mesenchymal Transition to Alleviate Renal Allograft Fibrosis Through Autophagy Activation

Fibrosis contributes to graft loss in chronic renal allograft injury. Endothelial‐to‐mesenchymal transition (EndMT) plays an important role in the development of fibrosis following kidney transplantation. Autophagy plays an important role in the homeostasis of diverse cell types including endothelia...

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Autores principales:	Jiajun Zhou, Mengtian Yao, Minghui Zhu, Mengchao Li, Qiwei Ke, Bing Wu, Daming Wang
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	endothelial‐to‐mesenchymal transition allograft fibrosis autophagy curcumin chronic allograft dysfunction Immunologic diseases. Allergy RC581-607
Acceso en línea:	https://doaj.org/article/6b6aad5e4a9245dd9da2937368caa98a
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spelling	oai:doaj.org-article:6b6aad5e4a9245dd9da2937368caa98a2021-12-01T09:06:19ZCurcumin Blunts IL-6 Dependent Endothelial‐to‐Mesenchymal Transition to Alleviate Renal Allograft Fibrosis Through Autophagy Activation1664-322410.3389/fimmu.2021.656242https://doaj.org/article/6b6aad5e4a9245dd9da2937368caa98a2021-05-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fimmu.2021.656242/fullhttps://doaj.org/toc/1664-3224Fibrosis contributes to graft loss in chronic renal allograft injury. Endothelial‐to‐mesenchymal transition (EndMT) plays an important role in the development of fibrosis following kidney transplantation. Autophagy plays an important role in the homeostasis of diverse cell types including endothelial cells. Here we demonstrate that inhibition of autophagy by treatment with 3-methyladenine (3-MA) or by silencing autophagy-related (ATG)5 promoted interleukin (IL)-6–dependent EndMT in human umbilical vein endothelial cells (HUVECs) and human renal glomerular endothelial cells (HRGECs), and autophagy inactivation was associated with EndMT in patients with chronic allograft dysfunction. IL-6 level was significantly higher in the culture medium of HUVECs transfected with ATG5 siRNA or treated with 3-MA compared to the respective control groups. IL-6 application induced EndMT in HUVECs and HRGECs, whereas antibody-mediated neutralization of IL-6 suppressed EndMT induced by ATG5 silencing. The protective role of curcumin (Cur) against allograft fibrosis was confirmed in a rat kidney transplantation model of F344 donors to Lewis recipients. Curcumin—a natural polyphenol compound with known antifibrotic effects in various tissues—alleviated IL-6–induced EndMT and promoted autophagy in the allografted organ and in HUVECs. This is the first demonstration of the role of autophagy in renal allograft fibrosis; our findings indicate that curcumin can alleviate chronic renal allograft injury by suppressing IL-6–dependent EndMT via activation of autophagy.Jiajun ZhouMengtian YaoMinghui ZhuMengchao LiQiwei KeBing WuDaming WangFrontiers Media S.A.articleendothelial‐to‐mesenchymal transitionallograft fibrosisautophagycurcuminchronic allograft dysfunctionImmunologic diseases. AllergyRC581-607ENFrontiers in Immunology, Vol 12 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	endothelial‐to‐mesenchymal transition allograft fibrosis autophagy curcumin chronic allograft dysfunction Immunologic diseases. Allergy RC581-607
spellingShingle	endothelial‐to‐mesenchymal transition allograft fibrosis autophagy curcumin chronic allograft dysfunction Immunologic diseases. Allergy RC581-607 Jiajun Zhou Mengtian Yao Minghui Zhu Mengchao Li Qiwei Ke Bing Wu Daming Wang Curcumin Blunts IL-6 Dependent Endothelial‐to‐Mesenchymal Transition to Alleviate Renal Allograft Fibrosis Through Autophagy Activation
description	Fibrosis contributes to graft loss in chronic renal allograft injury. Endothelial‐to‐mesenchymal transition (EndMT) plays an important role in the development of fibrosis following kidney transplantation. Autophagy plays an important role in the homeostasis of diverse cell types including endothelial cells. Here we demonstrate that inhibition of autophagy by treatment with 3-methyladenine (3-MA) or by silencing autophagy-related (ATG)5 promoted interleukin (IL)-6–dependent EndMT in human umbilical vein endothelial cells (HUVECs) and human renal glomerular endothelial cells (HRGECs), and autophagy inactivation was associated with EndMT in patients with chronic allograft dysfunction. IL-6 level was significantly higher in the culture medium of HUVECs transfected with ATG5 siRNA or treated with 3-MA compared to the respective control groups. IL-6 application induced EndMT in HUVECs and HRGECs, whereas antibody-mediated neutralization of IL-6 suppressed EndMT induced by ATG5 silencing. The protective role of curcumin (Cur) against allograft fibrosis was confirmed in a rat kidney transplantation model of F344 donors to Lewis recipients. Curcumin—a natural polyphenol compound with known antifibrotic effects in various tissues—alleviated IL-6–induced EndMT and promoted autophagy in the allografted organ and in HUVECs. This is the first demonstration of the role of autophagy in renal allograft fibrosis; our findings indicate that curcumin can alleviate chronic renal allograft injury by suppressing IL-6–dependent EndMT via activation of autophagy.
format	article
author	Jiajun Zhou Mengtian Yao Minghui Zhu Mengchao Li Qiwei Ke Bing Wu Daming Wang
author_facet	Jiajun Zhou Mengtian Yao Minghui Zhu Mengchao Li Qiwei Ke Bing Wu Daming Wang
author_sort	Jiajun Zhou
title	Curcumin Blunts IL-6 Dependent Endothelial‐to‐Mesenchymal Transition to Alleviate Renal Allograft Fibrosis Through Autophagy Activation
title_short	Curcumin Blunts IL-6 Dependent Endothelial‐to‐Mesenchymal Transition to Alleviate Renal Allograft Fibrosis Through Autophagy Activation
title_full	Curcumin Blunts IL-6 Dependent Endothelial‐to‐Mesenchymal Transition to Alleviate Renal Allograft Fibrosis Through Autophagy Activation
title_fullStr	Curcumin Blunts IL-6 Dependent Endothelial‐to‐Mesenchymal Transition to Alleviate Renal Allograft Fibrosis Through Autophagy Activation
title_full_unstemmed	Curcumin Blunts IL-6 Dependent Endothelial‐to‐Mesenchymal Transition to Alleviate Renal Allograft Fibrosis Through Autophagy Activation
title_sort	curcumin blunts il-6 dependent endothelial‐to‐mesenchymal transition to alleviate renal allograft fibrosis through autophagy activation
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/6b6aad5e4a9245dd9da2937368caa98a
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Curcumin Blunts IL-6 Dependent Endothelial‐to‐Mesenchymal Transition to Alleviate Renal Allograft Fibrosis Through Autophagy Activation

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