Abstract
Liver provides insights into the mechanisms that control growth in a differentiated tissue. Rat liver regenerates its lost cells within 4 d of a 70% hepatectomy (PH). Hepatic mRNA for TGP-α, a mitogen for various liver cells, increases after PH. To test the hypothesis liver growth is regulated by increased concentrations of TGF-α peptide, we developed a highly specific RIA for rat TGF-α. Livers from male S.-D. rats (n=5 per group) after a 70% PH or sham hepatectomy (SH) were extracted in a low ionic strength buffer (pH 8) containing detergents and protease inhibitors. An increase in TGF-α peptide (p<0.02) in PH animals over SH controls was attained at 17 h, coincident with the onset of DNA synthesis. Two-fold elevations in peptide were maintained until 96 h, then lost by 8 d. Liver extracts were cliromatographed on Biogel P-60: In samples from sham-operated as well as DNA replicating (17 h) liver, TGF-α immunoactivity in was present exclusively as 18-40 kD precursors. Not until late proliferative (48 h), and post-regeneration (90 h) liver, did a significant fraction of ihe TGF-α appear as the mature 5.6 kD protein. Both transcriptional and post-translatioal controls appear evident in the regulation of TGF-α after PH: only precursor forms are present in quiescent and S-pluse liver, while mature TGF-α is detected only after the major proliferative response. The functions and/or target cells of precursor and mature forms of TGF-α may differ in liver, and the conversion of TGF-α precursors to mature peptide may be regulated by signals initialed by PH.
Article PDF
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Russell, W., Sitaric, S., Peck, A. et al. MULTIPLE LEVELS OF TGF-α MODULATION DURING RAT LIVER REGENERATION. Pediatr Res 33 (Suppl 5), S67 (1993). https://doi.org/10.1203/00006450-199305001-00383
Issue Date:
DOI: https://doi.org/10.1203/00006450-199305001-00383