PMID- 15514164
OWN - NLM
STAT- MEDLINE
DCOM- 20050615
LR  - 20211203
IS  - 1524-4571 (Electronic)
IS  - 0009-7330 (Linking)
VI  - 95
IP  - 11
DP  - 2004 Nov 26
TI  - RNA-binding proteins heterogeneous nuclear ribonucleoprotein A1, E1, and K are 
      involved in post-transcriptional control of collagen I and III synthesis.
PG  - 1058-66
AB  - Collagen types I and III, coded by COL1A1/COL1A2 and COL3A1 genes, are the major 
      fibrillar collagens produced by fibroblasts, including cardiac fibroblasts of the 
      adult heart. Characteristic for different cardiomyopathies is a remodeling 
      process associated with an upregulation of collagen synthesis, which leads to 
      fibrosis. We report identification of three mRNA-binding proteins, heterogeneous 
      nuclear ribonucleoprote (hnRNP) A1, E1, and K, as positive effectors of collagen 
      synthesis acting at the post-transcriptional level by interaction with the 
      3'-untranslated regions (3'-UTRs) of COL1A1, 1A2, and 3A1 mRNAs. In vitro, 
      binding experiments (electromobility shift assay and UV cross-linking) reveal 
      significant differences in binding to CU- and AU-rich binding motifs. Reporter 
      gene cell transfection experiments and RNA stability assays show that hnRNPs A1, 
      E1, and K stimulate collagen expression by stabilizing mRNAs. Collagen synthesis 
      is activated via the angiotensin II type 1 (AT1) receptor. We demonstrate that 
      transforming growth factor-beta1, a major product of stimulated AT1 receptor, 
      does not activate solely collagen synthesis but synergistically the synthesis of 
      hnRNP A1, E1, and K as well. Thus, post-transcriptional control of collagen 
      synthesis at the mRNA level may substantially be caused by alteration of the 
      expression of RNA-binding proteins. The pathophysiological impact of this finding 
      was demonstrated by screening the expression of hnRNP E1 and K in cardiovascular 
      diseases. In the heart muscle of patients experiencing aortic stenosis, ischemic 
      cardiomyopathy, or dilatative cardiomyopathy, a significant increase in the 
      expression of hnRNP E1, A1, and K was found between 1.5- and 4.5-fold relative to 
      controls.
FAU - Thiele, Bernd-Joachim
AU  - Thiele BJ
AD  - Institut fur Physiologie, University-Medicine Berlin, Germany.
FAU - Doller, Anke
AU  - Doller A
FAU - Kahne, Thilo
AU  - Kahne T
FAU - Pregla, Reinhard
AU  - Pregla R
FAU - Hetzer, Roland
AU  - Hetzer R
FAU - Regitz-Zagrosek, Vera
AU  - Regitz-Zagrosek V
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20041028
PL  - United States
TA  - Circ Res
JT  - Circulation research
JID - 0047103
RN  - 0 (3' Untranslated Regions)
RN  - 0 (COL3A1 protein, human)
RN  - 0 (Collagen Type I)
RN  - 0 (Collagen Type I, alpha 1 Chain)
RN  - 0 (Collagen Type III)
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (Heterogeneous Nuclear Ribonucleoprotein A1)
RN  - 0 (Heterogeneous-Nuclear Ribonucleoprotein Group A-B)
RN  - 0 (Heterogeneous-Nuclear Ribonucleoprotein K)
RN  - 0 (Heterogeneous-Nuclear Ribonucleoproteins)
RN  - 0 (PCBP1 protein, human)
RN  - 0 (RNA, Messenger)
RN  - 0 (RNA-Binding Proteins)
RN  - 0 (Receptor, Angiotensin, Type 1)
RN  - 0 (Recombinant Fusion Proteins)
RN  - 0 (Ribonucleoproteins)
RN  - 0 (TGFB1 protein, human)
RN  - 0 (Thymus Hormones)
RN  - 0 (Transforming Growth Factor beta)
RN  - 0 (Transforming Growth Factor beta1)
RN  - 0 (hnRNPA1 protein, human)
RN  - 146410-60-8 (HNRNPK protein, human)
RN  - 9007-34-5 (Collagen)
SB  - IM
MH  - 3' Untranslated Regions/*metabolism
MH  - Aortic Valve Stenosis/genetics/*metabolism
MH  - Base Sequence
MH  - Cardiomyopathy, Dilated/genetics/*metabolism
MH  - Cells, Cultured/drug effects/metabolism
MH  - Collagen/biosynthesis/*genetics
MH  - Collagen Type I/biosynthesis/*genetics
MH  - Collagen Type I, alpha 1 Chain
MH  - Collagen Type III/biosynthesis/*genetics
MH  - DNA-Binding Proteins
MH  - Fibroblasts/drug effects/metabolism
MH  - Gene Expression Regulation/*physiology
MH  - Heart Failure/metabolism/pathology
MH  - Heterogeneous Nuclear Ribonucleoprotein A1
MH  - Heterogeneous-Nuclear Ribonucleoprotein Group A-B
MH  - Heterogeneous-Nuclear Ribonucleoprotein K
MH  - Heterogeneous-Nuclear Ribonucleoproteins/metabolism/*physiology
MH  - Humans
MH  - Molecular Sequence Data
MH  - Myocardial Ischemia/genetics/*metabolism
MH  - Protein Binding
MH  - Protein Interaction Mapping
MH  - RNA, Messenger/biosynthesis
MH  - RNA-Binding Proteins
MH  - Receptor, Angiotensin, Type 1/physiology
MH  - Recombinant Fusion Proteins/metabolism
MH  - Ribonucleoproteins/metabolism/*physiology
MH  - Thymus Hormones/metabolism/*physiology
MH  - Transfection
MH  - Transforming Growth Factor beta/physiology
MH  - Transforming Growth Factor beta1
EDAT- 2004/10/30 09:00
MHDA- 2005/06/16 09:00
CRDT- 2004/10/30 09:00
PHST- 2004/10/30 09:00 [pubmed]
PHST- 2005/06/16 09:00 [medline]
PHST- 2004/10/30 09:00 [entrez]
AID - 01.RES.0000149166.33833.08 [pii]
AID - 10.1161/01.RES.0000149166.33833.08 [doi]
PST - ppublish
SO  - Circ Res. 2004 Nov 26;95(11):1058-66. doi: 10.1161/01.RES.0000149166.33833.08. 
      Epub 2004 Oct 28.