Athanasios Stavropoulos, Maria Xilouri and their colleagues recently published a study in the journal Cellular & Molecular Biology Letters

TGFβ-superfamily signaling plays an important role in liver growth, regeneration, and fibrosis, but its hepatocyte-specific mechanisms remain unclear. This study investigated how modulation of TGFβ signaling affects hepatocytes during liver fibrosis. Using adenoviral overexpression of Smad3 or Smad7 in mouse livers, along with TGFβ1-treated hepatosphere cultures and transcriptomic analyses, the researchers identified ribosome biogenesis as a key process regulated by TGFβ signaling. Activation of TGFβ signaling suppressed ribosomal assembly in hepatocytes, while its inhibition via Smad7 enhanced ribosome biogenesis, increased hepatic protein content, and activated nucleolar function without triggering p53. This effect was mediated through the p70S6K–S6RP axis independently of c-MYC, mTOR, and MAPK pathways. Analysis of human cirrhotic liver tissue confirmed an inverse relationship between TGFβ signaling and ribosome biogenesis. Meta-analysis of RNA-seq data further revealed that TGFβ regulates ribosome biogenesis in a cell type–specific manner, inhibiting it in hepatocytes while promoting it in hepatic stellate cells. Overall, the findings highlight a SMAD-dependent role of TGFβ signaling in controlling hepatocyte growth and energy homeostasis, which is critical for liver regeneration following injury and fibrosis.

Pubmed

TGFβ pathway represses hepatic ribosome biogenesis and protein synthesis by regulating p70S6K-S6RP proteins.
Stavropoulos A, Stamatopoulou V, Pavlos E, Manioudaki M, Sakellariou S, Stathopoulos C, Xilouri M.Cell Mol Biol Lett. 2026 Jan 16. doi: 10.1186/s11658-025-00853-0. Online ahead of print.PMID: 41545854 Free article.