Fibulin-6 regulates pro-fibrotic TGF-beta responses in neonatal mouse ventricular cardiac fibroblasts
2017 | journal article. A publication with affiliation to the University of Göttingen.
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Fibulin-6 regulates pro-fibrotic TGF-beta responses in neonatal mouse ventricular cardiac fibroblasts
Chowdhury, A.; Hasselbach, L.; Echtermeyer, F.; Jyotsana, N.; Theilmeier, G. & Herzog, C. (2017)
Scientific Reports, 7 art. 42725. DOI: https://doi.org/10.1038/srep42725
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- Authors
- Chowdhury, Arpita; Hasselbach, Lisa; Echtermeyer, Frank; Jyotsana, Nidhi; Theilmeier, Gregor; Herzog, Christine
- Abstract
- Fibulin-6, an essential component of extracellular matrix determines the architecture of cellular junctions in tissues undergoing strain. Increased expression and deposition of fibulin-6 facilitates fibroblast migration in response to TGF-beta, following myocardial infarction in mouse heart. The underlying mechanism still remains elusive. In conjunction with our previous study, we have now demonstrated that in fibulin-6 knockdown (KD) fibroblasts, not only TGF-beta dependent migration, but also stress fiber formation, cellular networking and subsequently fibroblast wound contraction is almost abrogated. SMAD dependent TGF-beta pathway shows similar to 75% decreased translocation of R-SMAD and co-SMAD into the nucleus upon fibulin-6 KD. Consequently, SMAD dependent pro-fibrotic gene expression is considerably down regulated to basal levels both in mRNA and protein. Also, investigating the non-SMAD pathways we observed a constitutive increase in pERK-levels in fibulin-6 KD fibroblast compared to control, but no change was seen in pAKT. Immunoprecipitation studies revealed 60% reduced interaction of TGF-beta receptor II and I (TGFRII and I) accompanied by diminished phosphorylation of TGFRI at serin165 in fibulin-6 KD cells. In conclusion, fibulin-6 plays an important role in regulating TGF-beta mediated responses, by modulating TGF-beta receptor dimerization and activation to further trigger downstream pathways.
- Issue Date
- 2017
- Status
- published
- Publisher
- Nature Publishing Group
- Journal
- Scientific Reports
- ISSN
- 2045-2322
- Sponsor
- Department of Experimental Anesthesiology, MHH; HBRS