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August 16, 2026AJP Gastrointestinal and Liver PhysiologyOpen Access

Integrated analyses of in vivo mouse models and liver organoids reveal MFG-E8-mediated protection against hepatocyte injury

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Authors

HBHeng-Fu Henry BuQJQianming JiangHGHua Geng

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Overview

In vivo and in vitro study demonstrates that MFG-E8 protects hepatocytes from ferroptotic injury in mice, highlighting its therapeutic potential for liver regeneration.

Key Points

  • To determine the expression pattern and functional role of MFG-E8 in hepatocyte injury, epithelial integrity, and liver regeneration.
  • Assessed MFG-E8 expression dynamics in a doxycycline-inducible hepatocyte apoptosis mouse model (3xTg-iHAP) via RNAScope-immunostain codetection.
  • Cultured 3D organoids and 2D monolayers from wild-type and Mfge8-knockout mice to evaluate epithelial stability, recombinant MFG-E8 rescue, and transcriptomic changes via RNA-seq.
  • Mfge8 mRNA and protein levels peaked at 48 hours following hepatocyte injury, shifting from baseline cholangiocyte localization to robust hepatocyte induction.
  • 2D monolayers from Mfge8-knockout mice exhibited cytopathic disintegration by day 5, which was partially rescued by recombinant MFG-E8 treatment.
  • Transcriptomic profiling revealed an ~8-fold upregulation of the ferroptosis-associated gene Hddc3 in Mfge8-deficient cultures.

Cite This Study

Bu et al. (2026) studied this question.

synapsesocial.com/papers/6a8179eff2fb91fc834ad702https://doi.org/10.1152/ajpgi.00079.2026
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