ArticleNature2025
RANK drives structured intestinal epithelial expansion during pregnancy.
Article in Nature, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed.
- Regional organization of nutrient absorption across the small intestine.Nature reviews. Gastroenterology & hepatology · 2026Review
- Article
- Protective maternal gut instincts.Nature · 2026Article
- Human inflammatory bowel disease-on-a-chip for modelling disease progression, cancer initiation and sex-specific effects.Nature biomedical engineering · 2026Article
- Rank-dependent control of tuft and BEST4 cell development in the intestine.Nature communications · 2026Article
- RANKL inhibits macrophage proinflammatory Toll-like receptor 2 and 4 signaling and impairs killing of intracellular bacteria.ImmunoHorizons · 2026Article
- Mating regulates growth, metabolism, and digestive efficiency in the femaleProceedings of the National Academy of Sciences of the United States of America · 2026Article
- Maternal Organ Growth: How the Adult Intestine Remodels During Pregnancy and Lactation.Development, growth & differentiation · 2026Review
- A clinical study of Simotang oral liquid combined with Shenque acupoint application for abdominal distension after cesarean section.Frontiers in medicine · 2026Article
- Genomic analysis unlocks the potential of denosumab as a targeted therapy for Crohn's disease.Scientific reports · 2025Article
- A cellular basis for heightened gut sensitivity in females.Science (New York, N.Y.) · 2025Article
- The Mediating Role of Bioactive Molecules in Gut Microbiota-Bone Metabolism Crosstalk.Nutrients · 2025Review
- Pregnancy induces intestinal epithelial elongation and estriol-associated activation of the Hippo signaling pathway in a mouse model.Pflugers Archiv : European journal of physiology · 2025Article
- Trend analysis and epidemiological forecasting of colorectal Cancer mortality among reproductive-age women in sub-Saharan Africa.Preventive medicine reports · 2025Article
- Effects of the gut microbiota on placental angiogenesis and intrauterine growth in gnotobiotic mice.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Article
Corrections and comments
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Authors and funding
26 authors.
Funding
Abstract
During reproduction, multiple species such as insects and all mammals undergo extensive physiological and morphological adaptions to ensure health and survival of the mother and optimal development of the offspring. Here we report that the intestinal epithelium undergoes expansion during pregnancy and lactation in mammals. This enlargement of the intestinal surface area results in a novel geometry of expanded villi. Receptor activator of nuclear factor-κΒ (RANK, encoded by TNFRSF11A) and its ligand RANKL were identified as a molecular pathway involved in this villous expansion of the small intestine in vivo in mice and in intestinal mouse and human organoids. Mechanistically, RANK-RANKL protects gut epithelial cells from cell death and controls the intestinal stem cell niche through BMP receptor signalling, resulting in the elongation of villi and a prominent increase in the intestinal surface. As a transgenerational consequence, babies born to female mice that lack Rank in the intestinal epithelium show reduced weight and develop glucose intolerance after metabolic stress. Whereas gut epithelial remodelling in pregnancy/lactation is reversible, constitutive expression of an active form of RANK is sufficient to drive intestinal expansion followed by loss of villi and stem cells, and prevents the formation of Apc
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.