Schneider, Magdalena and Dillinger, Andrea E. and Ohlmann, Andreas and Iozzo, Renato and Fuchshofer, Rudolf (2021) Decorin-An Antagonist of TGF-beta in Astrocytes of the Optic Nerve. INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, 22 (14): 7660. ISSN 1422-0067
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During the pathogenesis of glaucoma, optic nerve (ON) axons become continuously damaged at the optic nerve head (ONH). This often is associated with reactive astrocytes and increased transforming growth factor (TGF-beta) 2 levels. In this study we tested the hypothesis if the presence or absence of decorin (DCN), a small leucine-rich proteoglycan and a natural inhibitor of several members of the TGF family, would affect the expression of the TGF-beta s and connective tissue growth factor (CTGF/CCN2) in human ONH astrocytes and murine ON astrocytes. We found that DCN is present in the mouse ON and is expressed by human ONH and murine ON astrocytes. DCN expression and synthesis was significantly reduced after 24 h treatment with 3 nM CTGF/CCN2, while treatment with 4 pM TGF-beta 2 only reduced expression of DCN significantly. Conversely, DCN treatment significantly reduced the expression of TGF-beta 1, TGF-beta 2 and CTGF/CCN2 vis-a-vis untreated controls. Furthermore, DCN treatment significantly reduced expression of fibronectin (FN) and collagen IV (COL IV). Notably, combined treatment with DCN and triciribine, a small molecule inhibitor of protein kinase B (AKT), attenuated effects of DCN on CTGF/CCN2, TGF-beta 1, and TGF-beta 2 mRNA expression. We conclude (1) that DCN is an important regulator of TGF-beta and CTGF/CCN2 expression in astrocytes of the ON and ONH, (2) that DCN thereby regulates the expression of extracellular matrix (ECM) components and (3) that DCN executes its negative regulatory effects on TGF-beta and CTGF/CCN2 via the pAKT/AKT signaling pathway in ON astrocytes.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | GROWTH-FACTOR-BETA; ELEVATED INTRAOCULAR-PRESSURE; HUMAN LAMINA-CRIBROSA; GENE-EXPRESSION; MARFAN-SYNDROME; TRANSFORMING GROWTH-FACTOR-BETA-1; TRABECULAR MESHWORK; AQUEOUS-HUMOR; HEAD; COLLAGEN; glaucoma; astrocytes; decorin; TGF-beta; reactive gliosis; optic nerve head; CTGF/CCN2; AKT signaling |
| Subjects: | 500 Science > 570 Life sciences |
| Divisions: | Biology, Preclinical Medicine > Institut für Anatomie > Lehrstuhl für Humananatomie und Embryologie |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 05 Jul 2022 06:04 |
| Last Modified: | 05 Jul 2022 06:04 |
| URI: | https://pred.uni-regensburg.de/id/eprint/46863 |
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