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
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 co...
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MDPI AG
2020-07-01
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| author | Gry H. Dihazi Marwa Eltoweissy Olaf Jahn Björn Tampe Michael Zeisberg Hauke S. Wülfrath Gerhard A. Müller Hassan Dihazi |
| author_facet | Gry H. Dihazi Marwa Eltoweissy Olaf Jahn Björn Tampe Michael Zeisberg Hauke S. Wülfrath Gerhard A. Müller Hassan Dihazi |
| author_sort | Gry H. Dihazi |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-10T18:23:35Z |
| format | Article |
| id | doaj.art-44dee0392baf41aebb7d5029c68f95e6 |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-10T18:23:35Z |
| publishDate | 2020-07-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-44dee0392baf41aebb7d5029c68f95e62023-11-20T07:12:20ZengMDPI AGCells2073-44092020-07-0197172410.3390/cells9071724The Secretome Analysis of Activated Human Renal Fibroblasts Revealed Beneficial Effect of the Modulation of the Secreted Peptidyl-Prolyl Cis-Trans Isomerase A in Kidney FibrosisGry H. Dihazi0Marwa Eltoweissy1Olaf Jahn2Björn Tampe3Michael Zeisberg4Hauke S. Wülfrath5Gerhard A. Müller6Hassan Dihazi7Institute for Clinical Chemistry/UMG-Laboratories, University Medical Center Göttingen, Robert-Koch-Strasse 40, D-37075 Göttingen, GermanyDepartment of Zoology, Faculty of Science, Alexandria University, Alexandria 21500, EgyptProteomics Group, Max-Planck-Institute of Experimental Medicine, Hermann-Rein-Strasse 3, D-37075 Göttingen, GermanyClinic for Nephrology and Rheumatology, University Medical Center Göttingen, Robert-Koch-Strasse 40, D-37075 Göttingen, GermanyClinic for Nephrology and Rheumatology, University Medical Center Göttingen, Robert-Koch-Strasse 40, D-37075 Göttingen, GermanyInstitute for Clinical Chemistry/UMG-Laboratories, University Medical Center Göttingen, Robert-Koch-Strasse 40, D-37075 Göttingen, GermanyClinic for Nephrology and Rheumatology, University Medical Center Göttingen, Robert-Koch-Strasse 40, D-37075 Göttingen, GermanyClinic for Nephrology and Rheumatology, University Medical Center Göttingen, Robert-Koch-Strasse 40, D-37075 Göttingen, GermanyThe 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.https://www.mdpi.com/2073-4409/9/7/1724secretomekidney fibrosisPPIAtransforming growth factor beta 1 (TGFβ1) |
| spellingShingle | Gry H. Dihazi Marwa Eltoweissy Olaf Jahn Björn Tampe Michael Zeisberg Hauke S. Wülfrath Gerhard A. Müller Hassan Dihazi 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 secretome kidney fibrosis PPIA transforming growth factor beta 1 (TGFβ1) |
| title | 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 |
| title_full | 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 |
| title_fullStr | 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 |
| title_full_unstemmed | 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 |
| title_short | 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 |
| title_sort | 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 |
| topic | secretome kidney fibrosis PPIA transforming growth factor beta 1 (TGFβ1) |
| url | https://www.mdpi.com/2073-4409/9/7/1724 |
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