Cargando…

Lysophosphatidic Acid Is a Proinflammatory Stimulus of Renal Tubular Epithelial Cells

Chronic kidney disease (CKD) refers to a spectrum of diseases defined by renal fibrosis, permanent alterations in kidney structure, and low glomerular-filtration rate. Prolonged epithelial-tubular damage involves a series of changes that eventually lead to CKD, highlighting the importance of tubular...

Descripción completa

Detalles Bibliográficos
Autores principales: Magkrioti, Christiana, Antonopoulou, Georgia, Fanidis, Dionysios, Pliaka, Vaia, Sakellaropoulos, Theodore, Alexopoulos, Leonidas G., Ullmer, Christoph, Aidinis, Vassilis
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9267536/
https://www.ncbi.nlm.nih.gov/pubmed/35806457
http://dx.doi.org/10.3390/ijms23137452
_version_ 1784743742713888768
author Magkrioti, Christiana
Antonopoulou, Georgia
Fanidis, Dionysios
Pliaka, Vaia
Sakellaropoulos, Theodore
Alexopoulos, Leonidas G.
Ullmer, Christoph
Aidinis, Vassilis
author_facet Magkrioti, Christiana
Antonopoulou, Georgia
Fanidis, Dionysios
Pliaka, Vaia
Sakellaropoulos, Theodore
Alexopoulos, Leonidas G.
Ullmer, Christoph
Aidinis, Vassilis
author_sort Magkrioti, Christiana
collection PubMed
description Chronic kidney disease (CKD) refers to a spectrum of diseases defined by renal fibrosis, permanent alterations in kidney structure, and low glomerular-filtration rate. Prolonged epithelial-tubular damage involves a series of changes that eventually lead to CKD, highlighting the importance of tubular epithelial cells in this process. Lysophosphatidic acid (LPA) is a bioactive lipid that signals mainly through its six cognate LPA receptors and is implicated in several chronic inflammatory pathological conditions. In this report, we have stimulated human proximal tubular epithelial cells (HKC-8) with LPA and 175 other possibly pathological stimuli, and simultaneously detected the levels of 27 intracellular phosphoproteins and 32 extracellular secreted molecules with multiplex ELISA. This quantification revealed a large amount of information concerning the signaling and the physiology of HKC-8 cells that can be extrapolated to other proximal tubular epithelial cells. LPA responses clustered with pro-inflammatory stimuli such as TNF and IL-1, promoting the phosphorylation of important inflammatory signaling hubs, including CREB1, ERK1, JUN, IκΒα, and MEK1, as well as the secretion of inflammatory factors of clinical relevance, including CCL2, CCL3, CXCL10, ICAM1, IL-6, and IL-8, most of them shown for the first time in proximal tubular epithelial cells. The identified LPA-induced signal-transduction pathways, which were pharmacologically validated, and the secretion of the inflammatory factors offer novel insights into the possible role of LPA in CKD pathogenesis.
format Online
Article
Text
id pubmed-9267536
institution National Center for Biotechnology Information
language English
publishDate 2022
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-92675362022-07-09 Lysophosphatidic Acid Is a Proinflammatory Stimulus of Renal Tubular Epithelial Cells Magkrioti, Christiana Antonopoulou, Georgia Fanidis, Dionysios Pliaka, Vaia Sakellaropoulos, Theodore Alexopoulos, Leonidas G. Ullmer, Christoph Aidinis, Vassilis Int J Mol Sci Article Chronic kidney disease (CKD) refers to a spectrum of diseases defined by renal fibrosis, permanent alterations in kidney structure, and low glomerular-filtration rate. Prolonged epithelial-tubular damage involves a series of changes that eventually lead to CKD, highlighting the importance of tubular epithelial cells in this process. Lysophosphatidic acid (LPA) is a bioactive lipid that signals mainly through its six cognate LPA receptors and is implicated in several chronic inflammatory pathological conditions. In this report, we have stimulated human proximal tubular epithelial cells (HKC-8) with LPA and 175 other possibly pathological stimuli, and simultaneously detected the levels of 27 intracellular phosphoproteins and 32 extracellular secreted molecules with multiplex ELISA. This quantification revealed a large amount of information concerning the signaling and the physiology of HKC-8 cells that can be extrapolated to other proximal tubular epithelial cells. LPA responses clustered with pro-inflammatory stimuli such as TNF and IL-1, promoting the phosphorylation of important inflammatory signaling hubs, including CREB1, ERK1, JUN, IκΒα, and MEK1, as well as the secretion of inflammatory factors of clinical relevance, including CCL2, CCL3, CXCL10, ICAM1, IL-6, and IL-8, most of them shown for the first time in proximal tubular epithelial cells. The identified LPA-induced signal-transduction pathways, which were pharmacologically validated, and the secretion of the inflammatory factors offer novel insights into the possible role of LPA in CKD pathogenesis. MDPI 2022-07-05 /pmc/articles/PMC9267536/ /pubmed/35806457 http://dx.doi.org/10.3390/ijms23137452 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Magkrioti, Christiana
Antonopoulou, Georgia
Fanidis, Dionysios
Pliaka, Vaia
Sakellaropoulos, Theodore
Alexopoulos, Leonidas G.
Ullmer, Christoph
Aidinis, Vassilis
Lysophosphatidic Acid Is a Proinflammatory Stimulus of Renal Tubular Epithelial Cells
title Lysophosphatidic Acid Is a Proinflammatory Stimulus of Renal Tubular Epithelial Cells
title_full Lysophosphatidic Acid Is a Proinflammatory Stimulus of Renal Tubular Epithelial Cells
title_fullStr Lysophosphatidic Acid Is a Proinflammatory Stimulus of Renal Tubular Epithelial Cells
title_full_unstemmed Lysophosphatidic Acid Is a Proinflammatory Stimulus of Renal Tubular Epithelial Cells
title_short Lysophosphatidic Acid Is a Proinflammatory Stimulus of Renal Tubular Epithelial Cells
title_sort lysophosphatidic acid is a proinflammatory stimulus of renal tubular epithelial cells
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9267536/
https://www.ncbi.nlm.nih.gov/pubmed/35806457
http://dx.doi.org/10.3390/ijms23137452
work_keys_str_mv AT magkriotichristiana lysophosphatidicacidisaproinflammatorystimulusofrenaltubularepithelialcells
AT antonopoulougeorgia lysophosphatidicacidisaproinflammatorystimulusofrenaltubularepithelialcells
AT fanidisdionysios lysophosphatidicacidisaproinflammatorystimulusofrenaltubularepithelialcells
AT pliakavaia lysophosphatidicacidisaproinflammatorystimulusofrenaltubularepithelialcells
AT sakellaropoulostheodore lysophosphatidicacidisaproinflammatorystimulusofrenaltubularepithelialcells
AT alexopoulosleonidasg lysophosphatidicacidisaproinflammatorystimulusofrenaltubularepithelialcells
AT ullmerchristoph lysophosphatidicacidisaproinflammatorystimulusofrenaltubularepithelialcells
AT aidinisvassilis lysophosphatidicacidisaproinflammatorystimulusofrenaltubularepithelialcells