PMID- 12595493
OWN - NLM
STAT- MEDLINE
DCOM- 20030811
LR  - 20190607
IS  - 1046-6673 (Print)
IS  - 1046-6673 (Linking)
VI  - 14
IP  - 3
DP  - 2003 Mar
TI  - Differential contribution of three mitogen-activated protein kinases to 
      PDGF-BB-induced mesangial cell proliferation and gene expression.
PG  - 584-92
AB  - This study examined the role of mitogen-activated protein (MAP) kinase in 
      PDGF-BB-induced proliferation and gene expression of human mesangial cells (MC). 
      PDGF-BB stimulation of MC increased mRNA for transforming growth factor-beta1 
      (TGF-beta1), monocyte chemoattractant protein-1 (MCP-1), and plasminogen 
      activator inhibitor-1 (PAI-1) and increased the cell numbers. To inhibit 
      activation of extracellular signal-regulated kinase (ERK), c-Jun amino-terminal 
      kinase (JNK), and p38, MC were infected with recombinant adenovirus containing 
      dominant-negative mutants of ERK, JNK, and p38 (Ad-DN-ERK, Ad-DN-JNK, Ad-DN-p38, 
      respectively), respectively. Infection of MC with Ad-DN-ERK or Ad-DN-JNK 
      inhibited PDGF-BB-induced increase in [(3)H]thymidine incorporation and cell 
      numbers, whereas Ad-DN-p38 did not. Ad-DN-ERK inhibited MCP-1 and PAI-1 mRNA 
      expression in MC, but not TGF-beta1. Ad-DN-JNK and Ad-DN-p38 inhibited TGF-beta1 
      and MCP-1 mRNA expression, but not PAI-1. The inhibition of activator protein-1 
      (AP-1) in MC, by adenovirus containing dominant-negative mutant of c-Jun 
      (Ad-DN-c-Jun), inhibited PDGF-BB-induced cell proliferation and TGF-beta1, MCP-1, 
      and PAI-1 expressions. Furthermore, Ad-DN-JNK or Ad-DN-p38, but not Ad-DN-ERK, 
      attenuated PDGF-BB-induced AP-1 activation in MC, indicating the involvement of 
      JNK and p38 in AP-1 activation. Our results indicated that ERK and JNK, but not 
      p38, participated in PDGF-BB-induced MC proliferation. PDGF-BB-induced expression 
      of TGF-beta1 was mediated by JNK and p38, MCP-1 expression was through ERK, JNK, 
      and p38, whereas PAI-1 expression was due to only ERK. AP-1 activation, which was 
      partially due to JNK and p38 activations, was involved in MC proliferation and 
      these three gene expressions. Thus, three MAP kinases seem to contribute to 
      progression of glomerular disease via different molecular mechanisms.
FAU - Kawano, Hitomi
AU  - Kawano H
AD  - Department of Pharmacology, Osaka City University Medical School, Japan.
FAU - Kim, Shokei
AU  - Kim S
FAU - Ohta, Kensuke
AU  - Ohta K
FAU - Nakao, Takafumi
AU  - Nakao T
FAU - Miyazaki, Hitoshi
AU  - Miyazaki H
FAU - Nakatani, Tatsuya
AU  - Nakatani T
FAU - Iwao, Hiroshi
AU  - Iwao H
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Am Soc Nephrol
JT  - Journal of the American Society of Nephrology : JASN
JID - 9013836
RN  - 0 (Platelet-Derived Growth Factor)
RN  - 0 (Proto-Oncogene Proteins c-sis)
RN  - 0 (Recombinant Proteins)
RN  - 0 (Transcription Factor AP-1)
RN  - 1B56C968OA (Becaplermin)
RN  - EC 2.7.11.24 (JNK Mitogen-Activated Protein Kinases)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinases)
RN  - EC 2.7.11.24 (p38 Mitogen-Activated Protein Kinases)
SB  - IM
EIN - J Am Soc Nephrol. 2019 Aug;30(8):1550. PMID: 31366696
MH  - Adenoviridae/genetics
MH  - Becaplermin
MH  - Cell Division/drug effects/physiology
MH  - Cells, Cultured
MH  - Gene Expression Regulation, Enzymologic/drug effects/physiology
MH  - Gene Transfer Techniques
MH  - Glomerular Mesangium/cytology/*enzymology
MH  - Humans
MH  - JNK Mitogen-Activated Protein Kinases
MH  - Mitogen-Activated Protein Kinases/*genetics/*metabolism
MH  - Platelet-Derived Growth Factor/*pharmacology
MH  - Proto-Oncogene Proteins c-sis
MH  - Recombinant Proteins/genetics/metabolism
MH  - Transcription Factor AP-1/metabolism
MH  - p38 Mitogen-Activated Protein Kinases
EDAT- 2003/02/22 04:00
MHDA- 2003/08/12 05:00
CRDT- 2003/02/22 04:00
PHST- 2003/02/22 04:00 [pubmed]
PHST- 2003/08/12 05:00 [medline]
PHST- 2003/02/22 04:00 [entrez]
AID - 10.1097/01.asn.0000050415.97942.2f [doi]
PST - ppublish
SO  - J Am Soc Nephrol. 2003 Mar;14(3):584-92. doi: 10.1097/01.asn.0000050415.97942.2f.