PMID- 23429583
OWN - NLM
STAT- MEDLINE
DCOM- 20130705
LR  - 20220331
IS  - 1522-1547 (Electronic)
IS  - 0193-1857 (Print)
IS  - 0193-1857 (Linking)
VI  - 304
IP  - 9
DP  - 2013 May 1
TI  - BMP2 inhibits TGF-beta-induced pancreatic stellate cell activation and extracellular 
      matrix formation.
PG  - G804-13
LID - 10.1152/ajpgi.00306.2012 [doi]
AB  - Activation of pancreatic stellate cells (PSCs) by transforming growth factor 
      (TGF)-beta is the key step in the development of pancreatic fibrosis, a common 
      pathological feature of chronic pancreatitis (CP). Bone morphogenetic proteins 
      (BMPs), members of the TGF-beta superfamily, have anti-fibrogenic functions, in 
      contrast to TGF-beta, in the kidney, lung, and liver. However, it is not known 
      whether BMPs have an anti-fibrogenic role in the pancreas. The current study was 
      designed to investigate the potential anti-fibrogenic role of BMPs in the 
      pancreas using an in vivo CP model and an in vitro PSC model. CP was induced by 
      repetitive intraperitoneal injections of cerulein in adult Swiss Webster mice. 
      The control mice received saline injections. Compared with the control, cerulein 
      injections induced a time-dependent increase in acinar injury and progression of 
      fibrosis and a steady increase in inflammation. Cerulein injections also induced 
      increases of the extracellular matrix (ECM) protein fibronectin and of alpha-smooth 
      muscle actin (alpha-SMA)-positive stellate cells (PSCs). The mice receiving cerulein 
      injections showed increased BMP2 protein levels and phosphorylated Smad1 levels 
      up to 4 wk and then declined at 8 wk to similar levels as the control. In vitro, 
      the isolated mouse and human PSCs were cultured and pretreated with BMP2 followed 
      by TGF-beta treatment. BMP2 pretreatment inhibited TGF-beta-induced alpha-SMA, fibronectin, 
      and collagen type Ia expression. Knocking down Smad1 with small-interfering RNA 
      reversed the inhibitory effect of BMP2 on TGF-beta-induced alpha-SMA and fibronectin 
      expression. Thus, BMP2 opposes the fibrogenic function of TGF-beta in PSCs through 
      the Smad1 signaling pathway.
FAU - Gao, Xuxia
AU  - Gao X
AD  - Department of Surgery, University of Texas Health Science Center-Houston, 
      Houston, TX 77026, USA.
FAU - Cao, Yanna
AU  - Cao Y
FAU - Yang, Wenli
AU  - Yang W
FAU - Duan, Chaojun
AU  - Duan C
FAU - Aronson, Judith F
AU  - Aronson JF
FAU - Rastellini, Cristiana
AU  - Rastellini C
FAU - Chao, Celia
AU  - Chao C
FAU - Hellmich, Mark R
AU  - Hellmich MR
FAU - Ko, Tien C
AU  - Ko TC
LA  - eng
GR  - P01-DK-035608/DK/NIDDK NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, U.S. Gov't, Non-P.H.S.
DEP - 20130221
PL  - United States
TA  - Am J Physiol Gastrointest Liver Physiol
JT  - American journal of physiology. Gastrointestinal and liver physiology
JID - 100901227
RN  - 0 (Actins)
RN  - 0 (Bone Morphogenetic Protein 2)
RN  - 0 (Fibronectins)
RN  - 0 (Smad1 Protein)
RN  - 0 (Smad1 protein, mouse)
RN  - 0 (Transforming Growth Factor beta)
RN  - 888Y08971B (Ceruletide)
SB  - IM
MH  - Actins/metabolism
MH  - Animals
MH  - Bone Morphogenetic Protein 2/*pharmacology
MH  - Ceruletide/pharmacology
MH  - Extracellular Matrix/metabolism
MH  - Female
MH  - Fibronectins/biosynthesis
MH  - Fibrosis
MH  - Humans
MH  - Mice
MH  - Pancreas/pathology
MH  - Pancreatic Stellate Cells/*drug effects
MH  - Pancreatitis, Chronic/chemically induced/pathology
MH  - Signal Transduction
MH  - Smad1 Protein/physiology
MH  - Transforming Growth Factor beta/antagonists & inhibitors/*pharmacology
PMC - PMC3652003
OTO - NOTNLM
OT  - bone morphogenetic protein
OT  - pancreas stellate cell
OT  - pancreatic fibrosis
OT  - transforming growth factor-beta
EDAT- 2013/02/23 06:00
MHDA- 2013/07/06 06:00
PMCR- 2014/05/01
CRDT- 2013/02/23 06:00
PHST- 2013/02/23 06:00 [entrez]
PHST- 2013/02/23 06:00 [pubmed]
PHST- 2013/07/06 06:00 [medline]
PHST- 2014/05/01 00:00 [pmc-release]
AID - ajpgi.00306.2012 [pii]
AID - GI-00306-2012 [pii]
AID - 10.1152/ajpgi.00306.2012 [doi]
PST - ppublish
SO  - Am J Physiol Gastrointest Liver Physiol. 2013 May 1;304(9):G804-13. doi: 
      10.1152/ajpgi.00306.2012. Epub 2013 Feb 21.