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Respective roles of the mitogen-activated protein kinase (MAPK) family members in pancreatic stellate cell activation induced by transforming growth factor-β1 (TGF-β1)
- Source :
- Biochemical and Biophysical Research Communications. 501:365-373
- Publication Year :
- 2018
- Publisher :
- Elsevier BV, 2018.
-
Abstract
- Activated pancreatic stellate cells (PSCs) play a crucial role in the progression of pancreatic fibrosis. Transforming growth factor-β (TGF-β) is one of the strongest stimulator inducing fibrosis. The mitogen-activated protein kinase (MAPK) proteins (including ERK, JNK and p38 MAPK) are known to contribute to PSC activation and pancreatic fibrosis. Previous studies have identified PSC activation induced by TGF-β1 is related to MAPK pathway, but the respective role of MAPK family members in PSC activation still unclear, and which family member may be the key mediator in mice PSC activation still controversial. In this study, we investigated the influence of different MAPK family member (JNK, ERK, and p38 MAPK) on mice PSC activation using an in vivo and in vitro model. The results showed p-JNK, p-ERK and p-p38 MAPK were all over-expressed in CP group, and p-JNK, p-ERK, and p-p38 MAPK were co-expressed with activated PSC. In vitro, TGF-β1 induced JNK and ERK over-expression in PSCs. In contrast, p38 MAPK expression in PSC showed only a very weak increase. JNK- and ERK-specific inhibitors inhibited FN and α-SMA mRNA expression in PSCs, and a p38 MAPK inhibitor had no effect on PSC activation. These findings indicate that JNK and ERK were directly involved in the PSCs activation induced by TGF-β1 and the development of pancreatic fibrosis. p38 MAPK participate in the progression of CP, but it does not respond to TGF-β1 directly and may not be regarded as the target of TGF-β1 induced PSC activation.
- Subjects :
- Male
0301 basic medicine
MAPK/ERK pathway
MAP Kinase Signaling System
p38 mitogen-activated protein kinases
Biophysics
Pancreatic stellate cell
Biochemistry
Gene Expression Regulation, Enzymologic
Transforming Growth Factor beta1
Mice
03 medical and health sciences
Fibrosis
Pancreatitis, Chronic
medicine
Animals
Protein kinase A
Protein Kinase Inhibitors
Molecular Biology
biology
Chemistry
Pancreatic Stellate Cells
Cell Biology
medicine.disease
Extracellular Matrix
030104 developmental biology
medicine.anatomical_structure
Mitogen-activated protein kinase
Hepatic stellate cell
Cancer research
biology.protein
Mitogen-Activated Protein Kinases
Receptors, Transforming Growth Factor beta
Transforming growth factor
Subjects
Details
- ISSN :
- 0006291X
- Volume :
- 501
- Database :
- OpenAIRE
- Journal :
- Biochemical and Biophysical Research Communications
- Accession number :
- edsair.doi.dedup.....287c521433bb8b12a5f7ab1e1b2b2d93