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bioRxiv · 10.64898/2026.01.26.701719

Ybx1 Deficiency Causes ROS-Driven IBD-Like Intestinal Inflammation and Postnatal Lethality

Zhu, B.·PARDESHI, L. A.·CHEN, Y.·Zhou, X.·Ge, W.
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Abstract

Y box-binding protein 1 (YB-1; Ybx1/ybx1) is essential for zebrafish development. Maternal ybx1-/- mutants exhibited embryonic lethality, whereas zygotic mutants (Zybx1-/-) showed high postnatal mortality between 10 and 20 dpf, although a small fraction survived to adulthood. Western blot and immunohistochemical analysis revealed strong, transient expression of Ybx1 in intestinal enterocytes from 3 to 5 days post-fertilization (dpf), followed by rapid ubiquitin-mediated degradation at 6 dpf, coinciding with defective intestinal development and compromised gut homeostasis. RNA-seq analysis identified elevated reactive oxygen species (ROS) and upregulation of matrix metalloproteinases mmp9 and mmp13a in Zybx1-/- larvae. Antioxidant treatment with ascorbic acid rescued postnatal lethality and alleviated intestinal defects, whereas prooxidant exposure exacerbated them. Pharmacological inhibition of Mmp9 or Mmp13a similarly prevented lethality, highlighting a ROS-MMP axis driving tissue damage. By 30 dpf, surviving mutants exhibited progressive intestinal impairment and severe pathology. These findings demonstrate that Ybx1 deficiency triggers ROS-dependent intestinal inflammation, MMP-mediated gut damage, and postnatal lethality, establishing Ybx1-deficient zebrafish as a robust model for studying inflammatory bowel disease (IBD)-like intestinal disorders.

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Zhu, B., PARDESHI, L. A., CHEN, Y., Zhou, X., Ge, W.. 2026-01-28. Ybx1 Deficiency Causes ROS-Driven IBD-Like Intestinal Inflammation and Postnatal Lethality. https://doi.org/10.64898/2026.01.26.701719

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