TY - JOUR
T1 - Interplay between extracellular matrix components and cellular and molecular mechanisms in kidney fibrosis
AU - Rayego-Mateos, Sandra
AU - Campillo, Sofia
AU - Rodrigues-Diez, Raúl R.
AU - Tejera-Muñoz, Antonio
AU - Marquez-Exposito, Laura
AU - Goldschmeding, Roel
AU - Rodríguez-Puyol, Diego
AU - Calleros, Laura
AU - Ruiz-Ortega, Marta
N1 - Funding Information:
This work was supported by the Instituto de Salud Carlos III (ISCIII) and Fondos FEDER European Union [grant numbers PI17/00119, PI20/00140, PI17/01513, PI17/00625, PI20/00634, PI20/00664, DTS20/00083]; the Red de Investigación Renal RED-INREN [grant number RD16/0009 (to M.R.-O. and D.R.-P.)]; the Sociedad Española de Nefrología, ‘NOVELREN-CM: Enfermedad renal crónica: nuevas Estrategias para la prevención, Diagnóstico y tratamiento’ [grant number B2017/BMD-3751 (to M.R.-O. and D.R.-P.)]; the ‘Convocatoria Dinamización Europa Investigación 2019’ MINECO [grant number EIN2019-103294 (to M.R.-O. and S.R.-M.)]; the ‘Juan de la Cierva Incorporación program’ from Ministerio de Economía, Industria y Competitividad (MINECO) [grant number IJC2018-035187-I (to S.R.-M.)]; the ‘ Sara Borrell’ program from Instituto de Salud Carlos III (ISCIII) [grant number CD20/00042 (to R.R.R-D.)]; the Innovation Programme under the Marie Sklodowska-Curie grant of the European Union’s Horizon 2020 [grant number IMProve-PD ID: 812699 (to M.R.-O.)].
Publisher Copyright:
© 2021 Portland Press Ltd. All rights reserved.
PY - 2021/8
Y1 - 2021/8
N2 - Chronic kidney disease (CKD) is characterized by pathological accumulation of extracellular matrix (ECM) proteins in renal structures. Tubulointerstitial fibrosis is observed in glomerular diseases as well as in the regeneration failure of acute kidney injury (AKI). Therefore, finding antifibrotic therapies comprises an intensive research field in Nephrology. Nowadays, ECM is not only considered as a cellular scaffold, but also exerts important cellular functions. In this review, we describe the cellular and molecular mechanisms involved in kidney fibrosis, paying particular attention to ECM components, profibrotic factors and cell–matrix interactions. In response to kidney damage, activation of glomerular and/or tubular cells may induce aberrant phenotypes characterized by overproduction of proinflammatory and profibrotic factors, and thus contribute to CKD progression. Among ECM components, matricellular proteins can regulate cell–ECM interactions, as well as cellular phenotype changes. Regarding kidney fibrosis, one of the most studied matricellular proteins is cellular communication network-2 (CCN2), also called connective tissue growth factor (CTGF), currently considered as a fibrotic marker and a potential therapeutic target. Integrins connect the ECM proteins to the actin cytoskeleton and several downstream signaling pathways that enable cells to respond to external stimuli in a coordinated manner and maintain optimal tissue stiffness. In kidney fibrosis, there is an increase in ECM deposition, lower ECM degradation and ECM proteins cross-linking, leading to an alteration in the tissue mechanical properties and their responses to injurious stimuli. A better understanding of these complex cellular and molecular events could help us to improve the antifibrotic therapies for CKD.
AB - Chronic kidney disease (CKD) is characterized by pathological accumulation of extracellular matrix (ECM) proteins in renal structures. Tubulointerstitial fibrosis is observed in glomerular diseases as well as in the regeneration failure of acute kidney injury (AKI). Therefore, finding antifibrotic therapies comprises an intensive research field in Nephrology. Nowadays, ECM is not only considered as a cellular scaffold, but also exerts important cellular functions. In this review, we describe the cellular and molecular mechanisms involved in kidney fibrosis, paying particular attention to ECM components, profibrotic factors and cell–matrix interactions. In response to kidney damage, activation of glomerular and/or tubular cells may induce aberrant phenotypes characterized by overproduction of proinflammatory and profibrotic factors, and thus contribute to CKD progression. Among ECM components, matricellular proteins can regulate cell–ECM interactions, as well as cellular phenotype changes. Regarding kidney fibrosis, one of the most studied matricellular proteins is cellular communication network-2 (CCN2), also called connective tissue growth factor (CTGF), currently considered as a fibrotic marker and a potential therapeutic target. Integrins connect the ECM proteins to the actin cytoskeleton and several downstream signaling pathways that enable cells to respond to external stimuli in a coordinated manner and maintain optimal tissue stiffness. In kidney fibrosis, there is an increase in ECM deposition, lower ECM degradation and ECM proteins cross-linking, leading to an alteration in the tissue mechanical properties and their responses to injurious stimuli. A better understanding of these complex cellular and molecular events could help us to improve the antifibrotic therapies for CKD.
KW - ccn2
KW - chronic kidney disease
KW - extracellular matrix components
KW - fibrosis
KW - integrins
KW - matricellular proteins
UR - http://www.scopus.com/inward/record.url?scp=85114187395&partnerID=8YFLogxK
U2 - 10.1042/CS20201016
DO - 10.1042/CS20201016
M3 - Review article
C2 - 34427291
AN - SCOPUS:85114187395
SN - 0143-5221
VL - 135
SP - 1999
EP - 2029
JO - Clinical Science
JF - Clinical Science
IS - 16
ER -