PUBLICATION
Diverse Signaling by TGFβ Isoforms in Response to Focal Injury is Associated with Either Retinal Regeneration or Reactive Gliosis
- Authors
- Conedera, F.M., Quintela Pousa, A.M., Presby, D.M., Mercader, N., Enzmann, V., Tschopp, M.
- ID
- ZDB-PUB-200403-199
- Date
- 2020
- Source
- Cellular and molecular neurobiology 41(1): 43-62 (Journal)
- Registered Authors
- Keywords
- Laser injury, Mouse, Müller cell, Reactive gliosis, Retinal regeneration, Tgf? signaling, Zebrafish
- MeSH Terms
-
- Gliosis/complications
- Gliosis/diagnostic imaging
- Gliosis/pathology*
- Protein Isoforms/metabolism
- Ependymoglial Cells/metabolism
- Ependymoglial Cells/pathology
- Plasminogen Activator Inhibitor 1/metabolism
- Up-Regulation
- Regeneration
- Signal Transduction*
- Mice, Transgenic
- Tomography, Optical Coherence
- Zebrafish
- Transforming Growth Factor beta/metabolism*
- Retinal Degeneration/complications
- Retinal Degeneration/diagnostic imaging
- Retinal Degeneration/pathology*
- Green Fluorescent Proteins/metabolism
- Fibrinolysis
- Lasers
- MAP Kinase Signaling System
- Animals
- Fibrosis
- Kinetics
- Transforming Growth Factor beta2/metabolism
- PubMed
- 32219603 Full text @ Cell. Mol. Neurobiol.
Citation
Conedera, F.M., Quintela Pousa, A.M., Presby, D.M., Mercader, N., Enzmann, V., Tschopp, M. (2020) Diverse Signaling by TGFβ Isoforms in Response to Focal Injury is Associated with Either Retinal Regeneration or Reactive Gliosis. Cellular and molecular neurobiology. 41(1):43-62.
Abstract
Müller cells may have stem cell-like capability as they regenerate photoreceptor loss upon injury in some vertebrates, but not in mammals. Indeed, mammalian Müller cells undergo major cellular and molecular changes summarized as reactive gliosis. Transforming growth factor beta (TGFβ) isoforms are multifunctional cytokines that play a central role, both in wound healing and in tissue repair. Here, we studied the role of TGFβ isoforms and their signaling pathways in response to injury induction during tissue regeneration in zebrafish and scar formation in mouse. Our transcriptome analysis showed a different activation of canonical and non-canonical signaling pathways and how they shaped the injury response. In particular, TGFβ3 promotes retinal regeneration via Smad-dependent canonical pathway upon regulation of junb gene family and mycb in zebrafish Müller cells. However, in mice, TGFβ1 and TGFβ2 evoke the p38MAPK signaling pathway. The activation of this non-canonical pathway leads to retinal gliosis. Thus, the regenerative versus reparative effect of the TGFβ pathway observed may rely on the activation of different signaling cascades. This provides one explanation of the different injury response in zebrafish and mouse retina.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping