Fuchs, Michaela A. A. and Broeker, Katharina A. E. and Schrankl, Julia and Burzlaff, Nicolai and Willam, Carsten and Wagner, Charlotte and Kurtz, Armin (2021) Inhibition of transforming growth factor beta 1 signaling in resident interstitial cells attenuates profibrotic gene expression and preserves erythropoietin production during experimental kidney fibrosis in mice. KIDNEY INTERNATIONAL, 100 (1). pp. 122-137. ISSN 0085-2538, 1523-1755
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Kidney fibrosis is characterized by the development of myofibroblasts originating from resident kidney and immigrating cells. Myofibroblast formation and extracellular matrix production during kidney damage are triggered by various cytokines. Among these, transforming growth factor beta 1 (TGF beta 1) is considered a central trigger for kidney fibrosis. We found a highly upregulated expression of TGF beta 1 and TGF beta receptor 2 (TGF beta-R2) mRNAs in kidney interstitial cells in experimental fibrosis. Here, we investigated the contribution of TGF beta 1 signaling in resident kidney interstitial cells to organ fibrosis using the models of adenine induced nephropathy and unilateral ureteral occlusion in mice. For this purpose TGF beta 1 signaling was interrupted by inducible deletion of the TGF beta-R2 gene in interstitial cells expressing the fibroblast marker platelet derived growth factor receptor-beta. Expression of profibrotic genes was attenuated up to 50% in kidneys lacking TGF beta-R2 in cells positive for platelet derived growth factor receptor-beta. Additionally, deletion of TGF beta-R2 prevented the decline of erythropoietin production in ureter ligated kidneys. Notably, fibrosis associated expression of alpha-smooth muscle actin as a myofibroblast marker and deposits of extracellular collagens were not altered in mice with targeted deletion of TGF beta-R2. Thus, our findings suggest an enhancing effect of TGF beta 1 signaling in resident interstitial cells that contributes to profibrotic gene expression and the downregulation of erythropoietin production, but not to the development of myofibroblasts during kidney fibrosis.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | TGF-BETA; RENAL FIBROSIS; DIVERSE ROLES; IN-VIVO; HYPOXIA; FIBROBLASTS; MECHANISMS; INJURY; ANEMIA; APOPTOSIS; erythropoietin; experimental kidney fibrosis; PDGFR-beta; renal interstitial cells; TGF beta |
| Subjects: | 500 Science > 570 Life sciences |
| Divisions: | Biology, Preclinical Medicine > Institut für Physiologie > Prof. Dr. Armin Kurtz |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 05 Sep 2022 08:30 |
| Last Modified: | 05 Sep 2022 08:30 |
| URI: | https://pred.uni-regensburg.de/id/eprint/46605 |
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