PMID- 14530074
OWN - NLM
STAT- MEDLINE
DCOM- 20040615
LR  - 20211203
IS  - 0142-9612 (Print)
IS  - 0142-9612 (Linking)
VI  - 24
IP  - 26
DP  - 2003 Nov
TI  - Enhanced DNA synthesis accompanied by constitutive phosphorylation of the ERK 
      pathway in human fibroblasts cultured on a polyelectrolyte complex.
PG  - 4771-6
AB  - In this study, we examined the cellular and molecular responses of fibroblasts 
      cultured on a polyelectrolyte complex (PEC) derived from sulfated chitin as a 
      polyanion and chitosan as a polycation. On PEC-coated dishes, the fibroblasts 
      aggregated and then developed spheroid-like structures. At earlier stages of 
      culture, DNA synthesis of cells cultured on PEC was stimulated approximately 75% 
      higher than control cells. Among various signaling molecules examined, including 
      mitogen-activated protein kinases, Akt/PKB and p53, an 
      extracellular-signal-regulated kinase (ERK) was selectively and constitutively 
      phosphorylated in cells cultured on PEC. The constitutive phosphorylation of ERK 
      was derived from an activation of the ERK kinase MEK, but not from an 
      inactivation of the ERK phosphatase MKP-1. Furthermore, ERK phosphorylation was 
      almost abolished by a membrane receptor tyrosine kinase inhibitor. The enhanced 
      phosphorylation of focal adhesion kinase, a downstream molecule of integrins, was 
      also observed in cells cultured on PEC. These results suggest that fibroblasts 
      recognize PEC as a continuous mitogenic stimulant which results in the 
      constitutive activation of the MEK-ERK pathway toward mitogenesis. Further, PEC 
      interacts with the cell membrane leading to activation of membrane molecules, 
      including integrins and receptor tyrosine kinases. These responses may account, 
      at least in part, for the potential use of PEC as a biomaterial for tissue 
      regeneration.
FAU - Matsuda, Naoki
AU  - Matsuda N
AD  - Center for Frontier Life Sciences, Nagasaki University, 1-12-4 Sakamoto, Nagasaki 
      852-8523, Japan. nuric@net.nagasaki-u.ac.jp
FAU - Horikawa, Miwa
AU  - Horikawa M
FAU - Yoshida, Masahiro
AU  - Yoshida M
FAU - Watanabe, Masami
AU  - Watanabe M
FAU - Nagahata, Misao
AU  - Nagahata M
FAU - Teramoto, Akira
AU  - Teramoto A
FAU - Abe, Koji
AU  - Abe K
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - Netherlands
TA  - Biomaterials
JT  - Biomaterials
JID - 8100316
RN  - 0 (Coated Materials, Biocompatible)
RN  - 0 (Electrolytes)
RN  - 0 (Proto-Oncogene Proteins)
RN  - 1398-61-4 (Chitin)
RN  - 9007-49-2 (DNA)
RN  - 9012-76-4 (Chitosan)
RN  - EC 2.7.11.1 (AKT1 protein, human)
RN  - EC 2.7.11.1 (Protein Serine-Threonine Kinases)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinases)
SB  - IM
MH  - Cell Aggregation/physiology
MH  - Cell Culture Techniques/*methods
MH  - Cell Differentiation/physiology
MH  - Cell Line
MH  - Chitin/*analogs & derivatives/*metabolism
MH  - Chitosan
MH  - Coated Materials, Biocompatible/metabolism
MH  - DNA/*biosynthesis
MH  - Electrolytes/metabolism
MH  - Fibroblasts/*cytology/*physiology
MH  - Humans
MH  - Mitogen-Activated Protein Kinases/*metabolism
MH  - Phosphorylation
MH  - *Protein Serine-Threonine Kinases
MH  - Proto-Oncogene Proteins/metabolism
MH  - Proto-Oncogene Proteins c-akt
MH  - Signal Transduction/*physiology
MH  - Tissue Engineering/methods
EDAT- 2003/10/08 05:00
MHDA- 2004/06/16 05:00
CRDT- 2003/10/08 05:00
PHST- 2003/10/08 05:00 [pubmed]
PHST- 2004/06/16 05:00 [medline]
PHST- 2003/10/08 05:00 [entrez]
AID - S0142961203003752 [pii]
AID - 10.1016/s0142-9612(03)00375-2 [doi]
PST - ppublish
SO  - Biomaterials. 2003 Nov;24(26):4771-6. doi: 10.1016/s0142-9612(03)00375-2.