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A two-hit model in biliary atresia: cooperative viral-bacterial activation of MMP7 via TLR4/NF-κB signaling

Pediatric Research (2025)Cite this article

Impact

  • Rhesus rotavirus (RRV) infection primes biliary epithelial cells to respond hyperactively to low-dose lipopolysaccharide (LPS), triggering upregulation of matrix metalloproteinase-7 (MMP7) via TLR4/NF-κB signaling.

  • Loss of endotoxin tolerance in biliary atresia (BA), associated with reduced expression of IRAK-M, leads to uncontrolled inflammation and tissue damage.

  • MMP7 acts as a dual-function molecule, contributing to both extracellular matrix remodeling and amplification of inflammatory signaling in BA.

  • Targeting the TLR4/NF-κB/MMP7 signaling axis represents a promising therapeutic strategy with potential applications in disease modification and early diagnosis of BA.

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Author information

Authors and Affiliations

  1. Department of Pediatrics, Assiut University, Assiut, Egypt

    Khaled Saad & Mostafa M. Embaby

  2. Department of Pediatrics, College of Medicine, Jouf University, Sakaka, Saudi Arabia

    Thamer A. M. Alruwaili

  3. Department of Community Health Nursing, Alddrab University College, Jazan University, Jazan, Saudi Arabia

    Amira Elhoufey

  4. Department of Community Health Nursing, Faculty of Nursing, Assiut University, Assiut, Egypt

    Amira Elhoufey

  5. Pediatric Intensive Care Unit, King Saud University Medical City, King Saud University, Riyadh, Saudi Arabia

    Mohamad-Hani Temsah

  6. Chemistry Department, Faculty of Science, Islamic University of Madinah, Madinah, Saudi Arabia

    Wesam M. Hussein

  7. Department of Pediatrics, Aswan University, Aswan, Egypt

    Mohamed Abdelsaboor

  8. Department of Pediatrics, Faculty of Medicine, Shaqra University, Dawadmi, Saudi Arabia

    Khalid Hashim Mahmoud

Authors
  1. Khaled Saad
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  2. Mostafa M. Embaby
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  3. Thamer A. M. Alruwaili
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  4. Amira Elhoufey
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  5. Mohamad-Hani Temsah
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  6. Wesam M. Hussein
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  7. Mohamed Abdelsaboor
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  8. Khalid Hashim Mahmoud
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Contributions

K.S. wrote and revised the commentary’s first draft; all authors revised the article critically and approved the final version to be published.

Corresponding author

Correspondence to Khaled Saad.

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The authors declare no competing interests.

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Saad, K., Embaby, M.M., Alruwaili, T.A.M. et al. A two-hit model in biliary atresia: cooperative viral-bacterial activation of MMP7 via TLR4/NF-κB signaling. Pediatr Res (2025). https://doi.org/10.1038/s41390-025-04242-3

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  • DOI: https://doi.org/10.1038/s41390-025-04242-3

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