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Mechanical Stretch Stimulates Cholangiocyte Proliferation and Profibrotic Gene Expression
Author(s) -
Munshi Md KAMRUZZAMAN,
Wise Candace,
Yang Fuquan,
Dostal David E.,
Glaser Shan S.
Publication year - 2010
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.24.1_supplement.1000.5
Subject(s) - endocrinology , medicine , cholangiocyte , ctgf , angiotensin ii receptor type 1 , angiotensin ii , chemistry , receptor , renin–angiotensin system , gene expression , biology , growth factor , gene , biochemistry , blood pressure
The angiotensin type 1 receptor (AT1) plays a key role in pressure‐induced vascular growth. AT1 also functions as a mechanoreceptor in addition to a GPCR. Although marked cholangiocyte proliferation occurs during obstructive cholestasis, a condition associated with increased biliary pressure, the role of AT1 in this process remains unclear. METHODS/RESULTS In vivo , administration of Ang II (50 ng/Kg/min) to normal and BDL rats resulted in a significant increase in PCNA positive cholangiocytes as compared to saline treated rats. PCNA increased 64% and 30% for normal and BDL treated with Ang II compared to controls, respectively. In vitro , Ang II increased NRIC (normal rat cholangiocyte) proliferation (maximal effect observed after 48 hrs at 10 −7 M Ang II (1.7‐fold)). This proliferation was mediated by AT1 as it is the only isoform expressed by rat cholangiocytes. To address the role of mechanical stress, NRIC were plated on BioFlex culture plates and static equiaxial strain was applied to the cells for 24 hrs. Mechanical strain increased NRIC growth (2‐fold) and expression of angiotensin converting enzyme (ACE) mRNA levels (19‐fold). Mechanical strain also increased CTGF, fibronectin 1, and NCAM1 profibrotic gene expression and Ang II secretion by 15%. CONCLUSION Ligand and mechanical activation of AT1 induces cholangiocyte growth and profibrotic gene expression.