ArticleThe Journal of clinical investigation2021
Dysregulation of mannose-6-phosphate-dependent cholesterol homeostasis in acinar cells mediates pancreatitis.
Article in The Journal of clinical investigation, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
18 citing papers in PubMed, 35 citations in OpenAlex.
- Genetic and pharmacologic modulations elucidate NRF2 protective role in acute pancreatitis.American journal of physiology. Gastrointestinal and liver physiology · 2026Article
- Conceptual framework and expert guidance on intrapancreatic fat deposition: the Melbourne consensus.Nature reviews. Gastroenterology & hepatology · 2026Review
- miR-1-3p, as a novel diagnostic and prognostic biomarker, aggravates pancreatic acinar cell injury in acute pancreatitis by targeting GNPTAB.Hereditas · 2026Article
- Antiaging Effects of Mannose-6-Phosphate through Enhanced Mitochondrial Function and Collagen Remodeling.ACS omega · 2026Article
- Reprogramming of cholesterol sensing in epithelial cells supports pancreatic inflammation.Molecular metabolism · 2026Article
- From single-pathway cascade to network pathophysiology: how genetically engineered mouse models reshaped our understanding of pancreatitis.Frontiers in physiology · 2026Review
- Pancreatic involvement inMolecular genetics and metabolism reports · 2025Article
- Effect of glycosylation on protein folding: From biological roles to chemical protein synthesis.iScience · 2025Review
- Causal mediation of plasma metabolomics in pancreatitis: A Mendelian randomization study.Medicine · 2025Article
- Trypsin in pancreatitis: The culprit, a mediator, or epiphenomenon?World journal of gastroenterology · 2024Review
- The integration of single-cell and bulk RNA-seq atlas reveals ERS-mediated acinar cell damage in acute pancreatitis.Journal of translational medicine · 2024Article
- Recent insights about autophagy in pancreatitis.eGastroenterology · 2024Article
- Autophagy and the pancreas: Healthy and disease states.Frontiers in cell and developmental biology · 2024Review
- Ethanol inhibits pancreatic acinar cell autophagy through upregulation of ATG4B, mediating pathological responses of alcoholic pancreatitis.American journal of physiology. Gastrointestinal and liver physiology · 2023Article
- Relationship between Cholesterol-Related Lipids and Severe Acute Pancreatitis: From Bench to Bedside.Journal of clinical medicine · 2023Review
- Association between autophagy and acute pancreatitis.Frontiers in genetics · 2023Review
- Characterization of temporospatial distribution of renal tubular casts by nephron tracking after ischemia-reperfusion injury.American journal of physiology. Renal physiology · 2022Article
- ATF3 induces RAB7 to govern autodegradation in paligenosis, a conserved cell plasticity program.EMBO reports · 2021Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
18 authors at 7 institutions in 3 countries.
Funding
Abstract
Disordered lysosomal/autophagy pathways initiate and drive pancreatitis, but the underlying mechanisms and links to disease pathology are poorly understood. Here, we show that the mannose-6-phosphate (M6P) pathway of hydrolase delivery to lysosomes critically regulates pancreatic acinar cell cholesterol metabolism. Ablation of the Gnptab gene encoding a key enzyme in the M6P pathway disrupted acinar cell cholesterol turnover, causing accumulation of nonesterified cholesterol in lysosomes/autolysosomes, its depletion in the plasma membrane, and upregulation of cholesterol synthesis and uptake. We found similar dysregulation of acinar cell cholesterol, and a decrease in GNPTAB levels, in both WT experimental pancreatitis and human disease. The mechanisms mediating pancreatic cholesterol dyshomeostasis in Gnptab-/- and experimental models involve a disordered endolysosomal system, resulting in impaired cholesterol transport through lysosomes and blockage of autophagic flux. By contrast, in Gnptab-/- liver the endolysosomal system and cholesterol homeostasis were largely unaffected. Gnptab-/- mice developed spontaneous pancreatitis. Normalization of cholesterol metabolism by pharmacologic means alleviated responses of experimental pancreatitis, particularly trypsinogen activation, the disease hallmark. The results reveal the essential role of the M6P pathway in maintaining exocrine pancreas homeostasis and function, and implicate cholesterol disordering in the pathogenesis of pancreatitis.
Indexed as
Identifiers
What OpenQuestion holds
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 OpenQuestion graph.