PMID- 16534498 OWN - NLM STAT- MEDLINE DCOM- 20060627 LR - 20230216 IS - 0023-6837 (Print) IS - 0023-6837 (Linking) VI - 86 IP - 5 DP - 2006 May TI - A potential role of somatostatin and its receptor SSTR4 in the migration of hepatic oval cells. PG - 477-89 AB - 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. FAU - Jung, Youngmi AU - Jung Y AD - Department of Pathology, Immunology and Laboratory Medicine, College of Medicine, University of Florida, Gainesville, FL 32610-0275, USA. FAU - Oh, Seh-Hoon AU - Oh SH FAU - Zheng, Donghang AU - Zheng D FAU - Shupe, Thomas D AU - Shupe TD FAU - Witek, Rafal P AU - Witek RP FAU - Petersen, Bryon E AU - Petersen BE LA - eng GR - DK058614/DK/NIDDK NIH HHS/United States GR - DK065096/DK/NIDDK NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PL - United States TA - Lab Invest JT - Laboratory investigation; a journal of technical methods and pathology JID - 0376617 RN - 0 (Antibodies) RN - 0 (Carcinogens) RN - 0 (Membrane Proteins) RN - 0 (Receptors, Somatostatin) RN - 0 (somatostatin receptor subtype-4) RN - 51110-01-1 (Somatostatin) RN - 9M98QLJ2DL (2-Acetylaminofluorene) SB - IM MH - 2-Acetylaminofluorene/pharmacology MH - Animals MH - Antibodies/pharmacology MH - Carcinogens/pharmacology MH - Cell Proliferation MH - Cells, Cultured MH - Chemotaxis MH - Disease Models, Animal MH - Hepatectomy MH - Hepatocytes/drug effects/*physiology MH - Liver/cytology/drug effects MH - Male MH - Membrane Proteins/immunology/*metabolism MH - Rats MH - Rats, Inbred F344 MH - Receptors, Somatostatin/immunology/*metabolism MH - Somatostatin/*physiology EDAT- 2006/03/15 09:00 MHDA- 2006/06/28 09:00 CRDT- 2006/03/15 09:00 PHST- 2006/03/15 09:00 [pubmed] PHST- 2006/06/28 09:00 [medline] PHST- 2006/03/15 09:00 [entrez] AID - S0023-6837(22)03282-2 [pii] AID - 10.1038/labinvest.3700410 [doi] PST - ppublish SO - Lab Invest. 2006 May;86(5):477-89. doi: 10.1038/labinvest.3700410.