Differential regulation of soluble guanylyl cyclase expression and signaling by collagens: involvement of integrin-linked kinase
Authors
Griera Merino, Mercedes; Frutos García, Sergio de; Saura Redondo, Marta; Rivero Vilches, Francisco Javier; Zaragoza Sánchez, Carlos; [et al.]Identifiers
Permanent link (URI): http://hdl.handle.net/10017/60976DOI: 10.1681/ASN.2004070587
ISSN: 1046-6673
Date
2005-07-16Affiliation
Universidad de Alcalá. Departamento de Biología de Sistemas; Universidad de Alcalá. Departamento de Medicina y Especialidades MédicasBibliographic citation
Journal of the American Society of Nephrology : JASN, 2005, v. 16, n. 9, p. 2626-2635
Document type
info:eu-repo/semantics/article
Version
info:eu-repo/semantics/aceptedVersion
Rights
Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0)
Access rights
info:eu-repo/semantics/openAccess
Abstract
Glomerular diseases are characterized by an abnormal synthesis of extracellular matrix proteins, such as collagen type I. Evidence that growth on collagen type I downregulates soluble guanylyl cyclase (sGC) expression and the responsiveness of human mesangial cells to nitric oxide (NO) by activating specific integrin signals involving integrin-linked kinase (ILK) is presented. Human mesangial cells were grown on collagen type I or IV for 24 to 72 h. Compared with collagen IV, growth on collagen I reduced the protein expression and NO-stimulated enzyme activity of sGC. This downregulation was effected at the level of transcription, because steady-state sGC mRNA expression was reduced on collagen I, but inhibition of transcription with Actinomycin D revealed no differences in transcript stability between the two culture conditions. Collagen I also reduced the capacity of cells to relax in response to NO after H2O2 challenge and inhibited NO-induced phosphorylation of vasodilator-activated phosphoprotein, a target of cyclic guanine monophosphate–dependent protein kinase. Examination of the surface expression of integrins, the receptors for extracellular matrix components, revealed that alfa1 and alfa2 integrin subunits were more abundant on cells that were grown on collagen IV and that surface expression of beta1 integrin did not vary with collagen type. However, growth on collagen I induced beta1 integrin to adopt its active conformation, and this activation of beta1 integrin was accompanied by increased activity of its downstream effector ILK. Dominant-negative suppression of ILK signaling relieved the suppression of sGC expression and NO-induced vasodilator-activated phosphoprotein phosphorylation induced by collagen I.
Files in this item
Files | Size | Format |
|
---|---|---|---|
Sergio_et_al_gcs_collagens_ilk ... | 1.121Mb |
|
Files | Size | Format |
|
---|---|---|---|
Sergio_et_al_gcs_collagens_ilk ... | 1.121Mb |
|
Collections
- FISIOLOG - Artículos [87]