ArticleGastroenterology2022
Malondialdehyde-Acetaldehyde Extracellular Matrix Protein Adducts Attenuate Unfolded Protein Response During Alcohol and Smoking-Induced Pancreatitis.
Article in Gastroenterology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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13 citing papers in PubMed, 24 citations in OpenAlex.
- A Metabolomics-Driven Integrated Machine Learning Framework for Early Prediction of Recurrent Acute Pancreatitis.Metabolites · 2026Article
- Cooperative Aldehyde Chemistry Maps an Orthogonal Lysine Reactivity Landscape.Journal of the American Chemical Society · 2026Article
- Bioengineering and omics approaches for Type 1 diabetes practical research: advancements and constraints.Annals of medicine · 2025Review
- Faecalibacterium prausnitzii alleviates experimental recurrent acute pancreatitis by producing oleic acid to regulate MAPK/NF-κB signaling and Th17/Treg balance.NPJ biofilms and microbiomes · 2025Article
- Global burden of acute pancreatitis attributable to high alcohol intake from 1990 to 2021: findings and prevention potential based on GBD 2021.BMC gastroenterology · 2025Article
- Inhibition of CDK5 signaling mediated inflammation in macrophages promotes cutaneous wound healing.Scientific reports · 2025Article
- Extracellular matrix dysregulation in aging, calcification, and cancer diseases: insights into cellular senescence, inflammation, and novel therapeutic strategies.International journal of biological sciences · 2025Review
- Global and regional burden of pancreatitis: epidemiological trends, risk factors, and projections to 2050 from the global burden of disease study 2021.BMC gastroenterology · 2024Article
- α-lipoic acid modulates prostate cancer cell growth and bone cell differentiation.Scientific reports · 2024Article
- Activation and Regulation of Pancreatic Stellate Cells in Chronic Pancreatic Fibrosis: A Potential Therapeutic Approach for Chronic Pancreatitis.Biomedicines · 2024Review
- Lipid peroxidation in osteoarthritis: focusing on 4-hydroxynonenal, malondialdehyde, and ferroptosis.Cell death discovery · 2023Review
- The East Asian-specific LPL p.Ala288Thr (c.862G > A) missense variant exerts a mild effect on protein function.Lipids in health and disease · 2023Article
- Causal link between gut microbiota and four types of pancreatitis: a genetic association and bidirectional Mendelian randomization study.Frontiers in microbiology · 2023Article
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16 authors at 2 institutions in 1 country.
Funding
Abstract
BACKGROUND &
aimsEpidemiological studies have established alcohol and smoking as independent risk factors for recurrent acute pancreatitis and chronic pancreatitis. However, the molecular players responsible for the progressive loss of pancreatic parenchyma and fibroinflammatory response are poorly characterized.
methodsTandem mass tag-based proteomic and bioinformatics analyses were performed on the pancreata of mice exposed to alcohol, cigarette smoke, or a combination of alcohol and cigarette smoke. Biochemical, immunohistochemistry, and transcriptome analyses were performed on the pancreatic tissues and primary acinar cells treated with cerulein in combination with ethanol (50 mmol/L) and cigarette smoke extract (40 μg/mL) for the mechanistic studies.
resultsA unique alteration in the pancreatic proteome was observed in mice exposed chronically to the combination of alcohol and cigarette smoke (56.5%) compared with cigarette smoke (21%) or alcohol (17%) alone. The formation of toxic metabolites (P < .001) and attenuated unfolded protein response (P < .04) were the significantly altered pathways on combined exposure. The extracellular matrix (ECM) proteins showed stable malondialdehyde-acetaldehyde (MAA) adducts in the pancreata of the combination group and chronic pancreatitis patients with a history of smoking and alcohol consumption. Interestingly, MAA-ECM adducts significantly suppressed expression of X-box-binding protein-1, leading to acinar cell death in the presence of alcohol and smoking. The stable MAA-ECM adducts persist even after alcohol and smoking cessation, and significantly delay pancreatic regeneration by abrogating the expression of cyclin-dependent kinases (CDK7 and CDK5) and regeneration markers.
conclusionsThe combined alcohol and smoking generate stable MAA-ECM adducts that increase endoplasmic reticulum stress and acinar cell death due to attenuated unfolded protein response and suppress expression of cell cycle regulators. Targeting aldehyde adducts might provide a novel therapeutic strategy for the management of recurrent acute pancreatitis and chronic pancreatitis.
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