PMID- 28209981
OWN - NLM
STAT- MEDLINE
DCOM- 20181024
LR  - 20181113
IS  - 2045-2322 (Electronic)
IS  - 2045-2322 (Linking)
VI  - 7
DP  - 2017 Feb 17
TI  - Fibulin-6 regulates pro-fibrotic TGF-beta responses in neonatal mouse ventricular 
      cardiac fibroblasts.
PG  - 42725
LID - 10.1038/srep42725 [doi]
LID - 42725
AB  - 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 ~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.
FAU - Chowdhury, Arpita
AU  - Chowdhury A
AD  - Department of Anesthesiology and Intensive Care Medicine, Hannover Medical 
      School, Hannover, Germany.
AD  - Department of Cellular Biochemistry, University Medical Center Gottingen, 
      Gottingen, Germany.
FAU - Hasselbach, Lisa
AU  - Hasselbach L
AD  - Department of Anesthesiology and Intensive Care Medicine, Hannover Medical 
      School, Hannover, Germany.
FAU - Echtermeyer, Frank
AU  - Echtermeyer F
AD  - Department of Anesthesiology and Intensive Care Medicine, Hannover Medical 
      School, Hannover, Germany.
FAU - Jyotsana, Nidhi
AU  - Jyotsana N
AD  - Department of Hematology, Hemostasis, Oncology and Stem cell Transplantation, 
      Hannover Medical School, Hannover, Germany.
FAU - Theilmeier, Gregor
AU  - Theilmeier G
AD  - Department of Anesthesiology and Intensive Care Medicine, Hannover Medical 
      School, Hannover, Germany.
AD  - Perioperative Inflammation and Infection, Department of Human Medicine, Faculty 
      of Medicine and Health Sciences, University of Oldenburg, Oldenburg, Germany.
FAU - Herzog, Christine
AU  - Herzog C
AD  - Department of Anesthesiology and Intensive Care Medicine, Hannover Medical 
      School, Hannover, Germany.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20170217
PL  - England
TA  - Sci Rep
JT  - Scientific reports
JID - 101563288
RN  - 0 (Extracellular Matrix Proteins)
RN  - 0 (Receptors, Transforming Growth Factor beta)
RN  - 0 (Smad Proteins)
RN  - 0 (Transforming Growth Factor beta)
RN  - 0 (hemicentin 1 protein, mouse)
SB  - IM
MH  - Animals
MH  - Cell Movement
MH  - Cells, Cultured
MH  - Extracellular Matrix Proteins/genetics/*metabolism
MH  - Fibroblasts/drug effects/*metabolism
MH  - Heart Ventricles/*cytology
MH  - MAP Kinase Signaling System
MH  - Mice
MH  - Receptors, Transforming Growth Factor beta/metabolism
MH  - Smad Proteins/metabolism
MH  - Stress Fibers/metabolism
MH  - Transforming Growth Factor beta/*pharmacology
PMC - PMC5314373
COIS- The authors declare no competing financial interests.
EDAT- 2017/02/18 06:00
MHDA- 2018/10/26 06:00
PMCR- 2017/02/17
CRDT- 2017/02/18 06:00
PHST- 2016/10/03 00:00 [received]
PHST- 2017/01/12 00:00 [accepted]
PHST- 2017/02/18 06:00 [entrez]
PHST- 2017/02/18 06:00 [pubmed]
PHST- 2018/10/26 06:00 [medline]
PHST- 2017/02/17 00:00 [pmc-release]
AID - srep42725 [pii]
AID - 10.1038/srep42725 [doi]
PST - epublish
SO  - Sci Rep. 2017 Feb 17;7:42725. doi: 10.1038/srep42725.