IL-15 Prevents Renal Fibrosis by Inhibiting Collagen Synthesis: A New Pathway in Chronic Kidney Disease?

Chronic kidney disease (CKD), secondary to renal fibrogenesis, is a public health burden. The activation of interstitial myofibroblasts and excessive production of extracellular matrix (ECM) proteins are major events leading to end-stage kidney disease. Recently, interleukin-15 (IL-15) has been impl...

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Autores principales:	Aurore Devocelle, Lola Lecru, Sophie Ferlicot, Thomas Bessede, Jean-Jacques Candelier, Julien Giron-Michel, Hélène François
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	chronic kidney disease fibrosis unilateral ureteral obstruction interleukin-15 myofibroblasts extracellular matrix Biology (General) QH301-705.5 Chemistry QD1-999
Acceso en línea:	https://doaj.org/article/26fc4420e4744069839a34941a507dae
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spelling	oai:doaj.org-article:26fc4420e4744069839a34941a507dae2021-11-11T17:09:33ZIL-15 Prevents Renal Fibrosis by Inhibiting Collagen Synthesis: A New Pathway in Chronic Kidney Disease?10.3390/ijms2221116981422-00671661-6596https://doaj.org/article/26fc4420e4744069839a34941a507dae2021-10-01T00:00:00Zhttps://www.mdpi.com/1422-0067/22/21/11698https://doaj.org/toc/1661-6596https://doaj.org/toc/1422-0067Chronic kidney disease (CKD), secondary to renal fibrogenesis, is a public health burden. The activation of interstitial myofibroblasts and excessive production of extracellular matrix (ECM) proteins are major events leading to end-stage kidney disease. Recently, interleukin-15 (IL-15) has been implicated in fibrosis protection in several organs, with little evidence in the kidney. Since endogenous IL-15 expression decreased in nephrectomized human allografts evolving toward fibrosis and kidneys in the unilateral ureteral obstruction (UUO) model, we explored IL-15’s renoprotective role by pharmologically delivering IL-15 coupled or not with its soluble receptor IL-15Rα. Despite the lack of effects on myofibroblast accumulation, both IL-15 treatments prevented tubulointerstitial fibrosis (TIF) in UUO as characterized by reduced collagen and fibronectin deposition. Moreover, IL-15 treatments inhibited collagen and fibronectin secretion by transforming growth factor-β (TGF-β)-treated primary myofibroblast cultures, demonstrating that the antifibrotic effect of IL-15 in UUO acts, in part, through a direct inhibition of ECM synthesis by myofibroblasts. In addition, IL-15 treatments resulted in decreased expression of monocyte chemoattractant protein 1 (MCP-1) and subsequent macrophage infiltration in UUO. Taken together, our study highlights a major role of IL-15 on myofibroblasts and macrophages, two main effector cells in renal fibrosis, demonstrating that IL-15 may represent a new therapeutic option for CKD.Aurore DevocelleLola LecruSophie FerlicotThomas BessedeJean-Jacques CandelierJulien Giron-MichelHélène FrançoisMDPI AGarticlechronic kidney diseasefibrosisunilateral ureteral obstructioninterleukin-15myofibroblastsextracellular matrixBiology (General)QH301-705.5ChemistryQD1-999ENInternational Journal of Molecular Sciences, Vol 22, Iss 11698, p 11698 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	chronic kidney disease fibrosis unilateral ureteral obstruction interleukin-15 myofibroblasts extracellular matrix Biology (General) QH301-705.5 Chemistry QD1-999
spellingShingle	chronic kidney disease fibrosis unilateral ureteral obstruction interleukin-15 myofibroblasts extracellular matrix Biology (General) QH301-705.5 Chemistry QD1-999 Aurore Devocelle Lola Lecru Sophie Ferlicot Thomas Bessede Jean-Jacques Candelier Julien Giron-Michel Hélène François IL-15 Prevents Renal Fibrosis by Inhibiting Collagen Synthesis: A New Pathway in Chronic Kidney Disease?
description	Chronic kidney disease (CKD), secondary to renal fibrogenesis, is a public health burden. The activation of interstitial myofibroblasts and excessive production of extracellular matrix (ECM) proteins are major events leading to end-stage kidney disease. Recently, interleukin-15 (IL-15) has been implicated in fibrosis protection in several organs, with little evidence in the kidney. Since endogenous IL-15 expression decreased in nephrectomized human allografts evolving toward fibrosis and kidneys in the unilateral ureteral obstruction (UUO) model, we explored IL-15’s renoprotective role by pharmologically delivering IL-15 coupled or not with its soluble receptor IL-15Rα. Despite the lack of effects on myofibroblast accumulation, both IL-15 treatments prevented tubulointerstitial fibrosis (TIF) in UUO as characterized by reduced collagen and fibronectin deposition. Moreover, IL-15 treatments inhibited collagen and fibronectin secretion by transforming growth factor-β (TGF-β)-treated primary myofibroblast cultures, demonstrating that the antifibrotic effect of IL-15 in UUO acts, in part, through a direct inhibition of ECM synthesis by myofibroblasts. In addition, IL-15 treatments resulted in decreased expression of monocyte chemoattractant protein 1 (MCP-1) and subsequent macrophage infiltration in UUO. Taken together, our study highlights a major role of IL-15 on myofibroblasts and macrophages, two main effector cells in renal fibrosis, demonstrating that IL-15 may represent a new therapeutic option for CKD.
format	article
author	Aurore Devocelle Lola Lecru Sophie Ferlicot Thomas Bessede Jean-Jacques Candelier Julien Giron-Michel Hélène François
author_facet	Aurore Devocelle Lola Lecru Sophie Ferlicot Thomas Bessede Jean-Jacques Candelier Julien Giron-Michel Hélène François
author_sort	Aurore Devocelle
title	IL-15 Prevents Renal Fibrosis by Inhibiting Collagen Synthesis: A New Pathway in Chronic Kidney Disease?
title_short	IL-15 Prevents Renal Fibrosis by Inhibiting Collagen Synthesis: A New Pathway in Chronic Kidney Disease?
title_full	IL-15 Prevents Renal Fibrosis by Inhibiting Collagen Synthesis: A New Pathway in Chronic Kidney Disease?
title_fullStr	IL-15 Prevents Renal Fibrosis by Inhibiting Collagen Synthesis: A New Pathway in Chronic Kidney Disease?
title_full_unstemmed	IL-15 Prevents Renal Fibrosis by Inhibiting Collagen Synthesis: A New Pathway in Chronic Kidney Disease?
title_sort	il-15 prevents renal fibrosis by inhibiting collagen synthesis: a new pathway in chronic kidney disease?
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/26fc4420e4744069839a34941a507dae
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IL-15 Prevents Renal Fibrosis by Inhibiting Collagen Synthesis: A New Pathway in Chronic Kidney Disease?

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