ArticleCell reports2021
The asymmetric Pitx2 gene regulates gut muscular-lacteal development and protects against fatty liver disease.
Article in Cell reports, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed, 17 citations in OpenAlex.
- Eosinophils promote a second wave of postnatal smooth muscle differentiation in intestinal villi.The Journal of cell biology · 2026Article
- Article
- Transport functions of intestinal lymphatic vessels.Nature reviews. Gastroenterology & hepatology · 2025Review
- TRIB3 Is a Hub Gene in Steatohepatitis and Aggravates Lipid Deposition and Inflammation in Hepatocytes.Diabetes, metabolic syndrome and obesity : targets and therapy · 2025Article
- Villus myofibroblasts are developmental and adult progenitors of mammalian gut lymphatic musculature.Developmental cell · 2024Article
- Intergenic sequences harboring potential enhancer elements contribute to Axenfeld-Rieger syndrome by regulating PITX2.JCI insight · 2024Article
- Mechanisms and functions of intestinal vascular specialization.The Journal of experimental medicine · 2024Review
- Chylomicrons Regulate Lacteal Permeability and Intestinal Lipid Absorption.Circulation research · 2023Article
- Endothelial FOXC1 and FOXC2 promote intestinal regeneration after ischemia-reperfusion injury.EMBO reports · 2023Article
- Brain-gut-liver axis: Chronic psychological stress promotes liver injury and fibrosisFrontiers in cellular and infection microbiology · 2022Article
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Authors and funding
12 authors at 2 institutions in 1 country.
Funding
Abstract
Intestinal lacteals are essential lymphatic channels for absorption and transport of dietary lipids and drive the pathogenesis of debilitating metabolic diseases. However, organ-specific mechanisms linking lymphatic dysfunction to disease etiology remain largely unknown. In this study, we uncover an intestinal lymphatic program that is linked to the left-right (LR) asymmetric transcription factor Pitx2. We show that deletion of the asymmetric Pitx2 enhancer ASE alters normal lacteal development through the lacteal-associated contractile smooth muscle lineage. ASE deletion leads to abnormal muscle morphogenesis induced by oxidative stress, resulting in impaired lacteal extension and defective lymphatic system-dependent lipid transport. Surprisingly, activation of lymphatic system-independent trafficking directs dietary lipids from the gut directly to the liver, causing diet-induced fatty liver disease. Our study reveals the molecular mechanism linking gut lymphatic function to the earliest symmetry-breaking Pitx2 and highlights the important relationship between intestinal lymphangiogenesis and the gut-liver axis.
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