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

Saad, Khaled; Embaby, Mostafa M; Alruwaili, Thamer A M; Elhoufey, Amira; Temsah, Mohamad-Hani; Hussein, Wesam M; Abdelsaboor, Mohamed; Mahmoud, Khalid Hashim · Pediatr Res · 2025

basic_science · Level V

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Abstract

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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