# Recombinant human thrombopoietin as a novel platelet-driven regulator accelerating hepatic regeneration in acute liver failure

## TL;DR

This study shows that recombinant human thrombopoietin improves liver recovery in rats with acute liver failure by boosting platelet counts and reducing inflammation.

## Contribution

The study introduces rhTPO as a novel platelet-driven regulator of liver regeneration in acute liver failure.

## Key findings

- rhTPO treatment increased platelet counts, liver growth factor, and reduced liver damage in rats.
- Transcriptomic and proteomic analyses revealed enhanced cell proliferation and reduced inflammation in the TPO group.
- Rats treated with rhTPO showed improved survival and liver function recovery compared to controls.

## Abstract

The aim of this study is to investigate the effect of recombinant human thrombopoietin (rhTPO) on liver regeneration in rats with acute liver failure (ALF) induced by D-galactosamine (D-GalN).

Sixty-six rats were divided into a control group and a TPO group. The control group received daily injections of normal saline, while the TPO group received daily injections of rhTPO. After five consecutive days of treatment, an ALF model was established in all rats via D-GalN administration. Survival status of the two groups was observed. Platelet count (PLT), liver function indicators, hepatocyte growth factor (HGF), and liver regeneration-related indicators were measured at different time points. Additionally, transcriptomic and proteomic analyses were performed on liver tissues.

Compared with the control group, the TPO group showed significantly higher levels of PLT, serum TPO, and HGF, milder liver tissue necrosis, a higher liver weight index, lower levels of alanine aminotransferase (ALT) and total bilirubin (TBil), and stronger liver regeneration capacity (as indicated by Ki67 and BrdU indices). Combined transcriptomic and proteomic analyses revealed that the expression of genes related to cell proliferation signaling pathways, such as Mapk1 and Map2k1, was significantly increased, while the expression of genes related to inflammatory pathways was significantly decreased.

rhTPO can promote the recovery of liver function and enhance liver regeneration in ALF rats by increasing PLT, stimulating cell proliferation, and inhibiting inflammation.

Diagram detailing an experimental setup. The top section shows randomized grouping of sixty-six mice into two groups: thirty-three receive rhTPO treatment and thirty-three receive saline, forming TPO and control groups. The middle section outlines the ALF animal models and sample collection timeline with specific dosages of D-GalN and sample collection points at baseline, six, twenty-four, and seventy-two hours. The bottom section describes dynamic detection methods, including liver function tests, blood analysis, ELISA, staining, and multi-omics analysis. There is a reference to survival observation with eight mice in each group.