Interplay between extracellular matrix components and cellular and molecular mechanisms in kidney fibrosis (2024)

Rayego-Mateos, S., Campillo, S., Rodrigues-Diez, R. R., Tejera-Muñoz, A., Marquez-Exposito, L., Goldschmeding, R., Rodríguez-Puyol, D., Calleros, L., & Ruiz-Ortega, M. (2021). Interplay between extracellular matrix components and cellular and molecular mechanisms in kidney fibrosis. Clinical Science, 135(16), 1999-2029. https://doi.org/10.1042/CS20201016

Rayego-Mateos, Sandra ; Campillo, Sofia ; Rodrigues-Diez, Raúl R. et al. / Interplay between extracellular matrix components and cellular and molecular mechanisms in kidney fibrosis. In: Clinical Science. 2021 ; Vol. 135, No. 16. pp. 1999-2029.

@article{e8f4b279909741a78af120cc83e1dfe5,

title = "Interplay between extracellular matrix components and cellular and molecular mechanisms in kidney fibrosis",

abstract = "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.",

keywords = "ccn2, chronic kidney disease, extracellular matrix components, fibrosis, integrins, matricellular proteins",

author = "Sandra Rayego-Mateos and Sofia Campillo and Rodrigues-Diez, {Ra{\'u}l R.} and Antonio Tejera-Mu{\~n}oz and Laura Marquez-Exposito and Roel Goldschmeding and Diego Rodr{\'i}guez-Puyol and Laura Calleros and Marta Ruiz-Ortega",

note = "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 Investigaci{\'o}n Renal RED-INREN [grant number RD16/0009 (to M.R.-O. and D.R.-P.)]; the Sociedad Espa{\~n}ola de Nefrolog{\'i}a, {\textquoteleft}NOVELREN-CM: Enfermedad renal cr{\'o}nica: nuevas Estrategias para la prevenci{\'o}n, Diagn{\'o}stico y tratamiento{\textquoteright} [grant number B2017/BMD-3751 (to M.R.-O. and D.R.-P.)]; the {\textquoteleft}Convocatoria Dinamizaci{\'o}n Europa Investigaci{\'o}n 2019{\textquoteright} MINECO [grant number EIN2019-103294 (to M.R.-O. and S.R.-M.)]; the {\textquoteleft}Juan de la Cierva Incorporaci{\'o}n program{\textquoteright} from Ministerio de Econom{\'i}a, Industria y Competitividad (MINECO) [grant number IJC2018-035187-I (to S.R.-M.)]; the {\textquoteleft} Sara Borrell{\textquoteright} 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{\textquoteright}s Horizon 2020 [grant number IMProve-PD ID: 812699 (to M.R.-O.)]. Publisher Copyright: {\textcopyright} 2021 Portland Press Ltd. All rights reserved.",

year = "2021",

month = aug,

doi = "10.1042/CS20201016",

language = "English",

volume = "135",

pages = "1999--2029",

journal = "Clinical Science",

issn = "0143-5221",

publisher = "Portland Press Ltd.",

number = "16",

}

Rayego-Mateos, S, Campillo, S, Rodrigues-Diez, RR, Tejera-Muñoz, A, Marquez-Exposito, L, Goldschmeding, R, Rodríguez-Puyol, D, Calleros, L & Ruiz-Ortega, M 2021, 'Interplay between extracellular matrix components and cellular and molecular mechanisms in kidney fibrosis', Clinical Science, vol. 135, no. 16, pp. 1999-2029. https://doi.org/10.1042/CS20201016

Interplay between extracellular matrix components and cellular and molecular mechanisms in kidney fibrosis. / Rayego-Mateos, Sandra; Campillo, Sofia; Rodrigues-Diez, Raúl R. et al.
In: Clinical Science, Vol. 135, No. 16, 08.2021, p. 1999-2029.

Research output: Contribution to journal › Review article › peer-review

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 -

Rayego-Mateos S, Campillo S, Rodrigues-Diez RR, Tejera-Muñoz A, Marquez-Exposito L, Goldschmeding R et al. Interplay between extracellular matrix components and cellular and molecular mechanisms in kidney fibrosis. Clinical Science. 2021 Aug;135(16):1999-2029. doi: 10.1042/CS20201016