The Secretome Analysis of Activated Human Renal Fibroblasts Revealed Beneficial Effect of the Modulation of the Secreted Peptidyl-Prolyl Cis-Trans Isomerase A in Kidney Fibrosis.
Cells
; 9(7)2020 07 18.
Article
en En
| MEDLINE
| ID: mdl-32708451
ABSTRACT
The secretome is an important mediator in the permanent process of reciprocity between cells and their environment. Components of secretome are involved in a large number of physiological mechanisms including differentiation, migration, and extracellular matrix modulation. Alteration in secretome composition may therefore trigger cell transformation, inflammation, and diseases. In the kidney, aberrant protein secretion plays a central role in cell activation and transition and in promoting renal fibrosis onset and progression. Using comparative proteomic analyses, we investigated in the present study the impact of cell transition on renal fibroblast cells secretome. Human renal cell lines were stimulated with profibrotic hormones and cytokines, and alterations in secretome were investigated using proteomic approaches. We identified protein signatures specific for the fibrotic phenotype and investigated the impact of modeling secretome proteins on extra cellular matrix accumulation. The secretion of peptidyl-prolyl cis-trans isomerase A (PPIA) was demonstrated to be associated with fibrosis phenotype. We showed that the in-vitro inhibition of PPIA with ciclosporin A (CsA) resulted in downregulation of PPIA and fibronectin (FN1) expression and significantly reduced their secretion. Knockdown studies of PPIA in a three-dimensional (3D) cell culture model significantly impaired the secretion and accumulation of the extracellular matrix (ECM), suggesting a positive therapeutic effect on renal fibrosis progression.
Palabras clave
Texto completo:
1
Base de datos:
MEDLINE
Asunto principal:
Isomerasa de Peptidilprolil
/
Proteoma
/
Fibroblastos
/
Riñón
Tipo de estudio:
Prognostic_studies
Límite:
Humans
Idioma:
En
Revista:
Cells
Año:
2020
Tipo del documento:
Article
País de afiliación:
Alemania