PMID- 11133005 OWN - NLM STAT- MEDLINE DCOM- 20010118 LR - 20190701 IS - 0024-3205 (Print) IS - 0024-3205 (Linking) VI - 67 IP - 24 DP - 2000 Nov 3 TI - Hypoxic conditions restore lost sensitivity to the growth inhibitory effect of transforming growth factor beta-1 (TGF beta-1) in proliferating rat hepatocytes in vitro. PG - 2929-40 AB - TGF beta-1 is known to be a growth inhibitor of regenerating liver, and an inducer of hepatocyte apoptosis in primary culture. However, hepatocytes can proliferate after partial hepatectomy even at high serum TGF beta-1 concentrations. In this study we used the primary cultures of rat hepatocytes for 10 days to investigate how TGF beta-1 affects proliferating hepatocytes. DNA synthesis peaked on day 8 of culture, and TGF beta-1-induced apoptosis was significantly suppressed on day 8 compared to days 2, 5, and 10. Flow-cytometric analysis revealed that hepatocytes that had incorporated BrdU were resistant to the apoptotic effect of TGF beta-1, and Northern blot analysis showed that TGF beta receptor mRNA was down-regulated on day 8. Hypoxic conditions restores TGF beta receptor mRNA expression and the lost sensitivity of proliferating hepatocyte to TGF beta-1. FAU - Kakihara, N AU - Kakihara N AD - The First Department of Surgery, Shiga University of Medical Science Seta-tsukinowacho, Otsu-city, Japan. kakihara@belle.shiga-med.ac.jp FAU - Takeshita, K AU - Takeshita K FAU - Ishibashi, H AU - Ishibashi H FAU - Tani, T AU - Tani T FAU - Kodama, M AU - Kodama M LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - Netherlands TA - Life Sci JT - Life sciences JID - 0375521 RN - 0 (RNA, Messenger) RN - 0 (Receptors, Transforming Growth Factor beta) RN - 0 (Transforming Growth Factor beta) RN - 9007-49-2 (DNA) RN - G34N38R2N1 (Bromodeoxyuridine) SB - IM MH - Animals MH - Apoptosis/drug effects MH - Blotting, Northern MH - Bromodeoxyuridine/metabolism MH - Cell Division MH - Cell Hypoxia/drug effects MH - Cells, Cultured MH - DNA/biosynthesis/drug effects MH - Down-Regulation MH - Flow Cytometry MH - Hepatocytes/cytology/*drug effects MH - In Situ Nick-End Labeling MH - Male MH - RNA, Messenger/metabolism MH - Rats MH - Rats, Inbred Lew MH - Receptors, Transforming Growth Factor beta/genetics/metabolism MH - Transforming Growth Factor beta/*pharmacology EDAT- 2001/01/02 11:00 MHDA- 2001/02/28 10:01 CRDT- 2001/01/02 11:00 PHST- 2001/01/02 11:00 [pubmed] PHST- 2001/02/28 10:01 [medline] PHST- 2001/01/02 11:00 [entrez] AID - S002432050000878X [pii] AID - 10.1016/s0024-3205(00)00878-x [doi] PST - ppublish SO - Life Sci. 2000 Nov 3;67(24):2929-40. doi: 10.1016/s0024-3205(00)00878-x.