A potential role of somatostatin and its receptor SSTR4 in the migration of hepatic oval cells.
Somatostatin (SST) is a regulatory peptide that activates G protein-coupled receptors comprised of five members (somatostatin receptors (SSTRs) 1-5). Despite the broad use of SST and its analogs in clinical practice, the spectrum of SST activities has been incompletely defined. Recently, it has been demonstrated that SST can be a chemoattractant for hematopoietic precursor cells. Since hepatic oval cells (HOCs) share common characteristics with hematopoietic stem cells, we hypothesized that SST could act as a chemoattractant for HOCs by stimulating SSTRs. Reverse transcriptase-polymerase chain reaction (RT-PCR) and Western blot assay revealed an increased expression of SST in the 2-acetyl-aminofluorene (2AAF)/partial hepatectomy (PHx) HOC induction model. Immunohistochemical staining showed the expression of SST in 2AAF/PHx-treated rat liver, as compared to normal liver. Proliferation and migration assays demonstrated that the increase of SST was related to migration of HOCs, but not their proliferation. RT-PCR and quantitative real-time PCR showed that SSTR4 was preferentially expressed by HOCs. Western blot assay and immunohistochemical staining confirmed the expression of SSTR4 by HOCs. In addition, pretreatment with anti-SSTR4 antibody cultures resulted in a dramatic reduction of cell migration as compared to that of control. Lastly, SST stimulated the rearrangement of actin filaments in HOCs, while HOCs treated with anti-SSTR4 antibody failed to do so. These results suggest a positive role for SST in the migration of HOCs, and that this effect is mediated through SSTR4.
Jung
Youngmi
Y
Department of Pathology, Immunology and Laboratory Medicine, College of Medicine, University of Florida, Gainesville, FL 32610-0275, USA.
Oh
Seh-Hoon
SH
Zheng
Donghang
D
Shupe
Thomas D
TD
Witek
Rafal P
RP
Petersen
Bryon E
BE
D015073:2-Acetylaminofluorene / Q000494:pharmacology; D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D002273:Carcinogens / Q000494:pharmacology; D049109:Cell Proliferation; D002478:Cells, Cultured; D002633:Chemotaxis; D004195:Disease Models, Animal; D006498:Hepatectomy; D022781:Hepatocytes / Q000187:drug effects / Q000502:physiology*; D008099:Liver / Q000166:cytology / Q000187:drug effects; D008297:Male; D008565:Membrane Proteins / Q000276:immunology / Q000378:metabolism*; D051381:Rats; D011916:Rats, Inbred F344; D017481:Receptors, Somatostatin / Q000276:immunology / Q000378:metabolism*; D013004:Somatostatin / Q000502:physiology*
D000906:Antibodies; D002273:Carcinogens; D008565:Membrane Proteins; D017481:Receptors, Somatostatin; C098681:somatostatin receptor subtype-4; D013004:Somatostatin; D015073:2-Acetylaminofluorene