{"doi":"10.1101/2020.03.25.008557","title":"Deficient ER Acetyl-CoA Import in Acinar Cells Leads to Chronic Pancreatitis","abstract":"Abstract Maintaining endoplasmic reticulum (ER) proteostasis is essential for pancreatic acinar cell function. Under conditions of severe ER stress, activation of pathogenic unfolded protein response pathways play a central role in the development and progression of pancreatitis. A key event in this pathogenic response is a loss of the transcription factor spliced XBP1 (XBP1s) and activation of the PERK pathway. Less is known of the consequence of perturbing ER-associated post-translational protein modification during pancreatitis. Here we show that expression of the ER acetyl-CoA transporter AT-1, necessary for ER protein acetylation, lies downstream of XBP1s and is significantly downregulated during the onset of pancreatitis. Genetic deletion of AT-1 in acinar cells of adult pancreas induces chronic ER stress marked by activation of both the XBP1s and PERK pathways, leading to mild/moderate chronic pancreatitis evidenced by accumulation of intracellular trypsin, immune cell infiltration, and fibrosis, but little pancreatic degeneration. Two-day induction of acute on chronic pancreatitis in AT-1 acinar specific knockout mice results in a severe CP phenotype with pronounced pancreatic atrophy. These findings uncover a new layer of complexity of the pathological ER stress response and its impact on pancreatic disease.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2020,"id":126421,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":1,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9596,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":343377,"name":"Diana D.H. Thomas","orcid":null,"position":1,"is_corresponding":false},{"id":426834,"name":"Katherine J. Deans","orcid":"0000-0002-4100-3262","position":2,"is_corresponding":false},{"id":573893,"name":"Yi Peng","orcid":"0000-0002-7042-9254","position":3,"is_corresponding":false},{"id":265036,"name":"Aurelia Lugea","orcid":null,"position":4,"is_corresponding":false},{"id":574343,"name":"S. J. Pandol","orcid":null,"position":5,"is_corresponding":false},{"id":299645,"name":"Luigi Puglielli","orcid":"0000-0003-0259-8424","position":6,"is_corresponding":false},{"id":343379,"name":"Guy E. Groblewski","orcid":null,"position":7,"is_corresponding":false},{"id":342220,"name":"Michelle Cooley","orcid":"0000-0003-3807-3240","position":0,"is_corresponding":true}],"reference_count":47,"raw_metadata":null,"created_at":"2026-07-18T23:15:23.509897Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}