Hepatic Protein and Phosphoprotein Signatures of Alcohol-Associated Cirrhosis and Hepatitis
| Autor: | Josiah Hardesty, Le Day, Jeffrey Warner, Dennis Warner, Marina Gritsenko, Aliya Asghar, Andrew Stolz, Timothy Morgan, Craig McClain, Jon Jacobs, Irina Kirpich |
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| Jazyk: | angličtina |
| Rok vydání: | 2022 |
| Předmět: |
Liver Cirrhosis
Proteomics Proteome Hepatitis Alcoholic Liver Diseases Liver Disease Chronic Liver Disease and Cirrhosis Regular Article Alcoholic Phosphoproteins Medical and Health Sciences Oral and gastrointestinal Hepatitis Pathology and Forensic Medicine Alcoholism Alcohol Use and Health Substance Misuse Good Health and Well Being 5.1 Pharmaceuticals Liver Cirrhosis Alcoholic Pathology Humans Development of treatments and therapeutic interventions Digestive Diseases Liver Diseases Alcoholic |
| Zdroj: | Am J Pathol The American journal of pathology, vol 192, iss 7 |
| Popis: | Alcohol-associated liver disease is a global health care burden, with alcohol-associated cirrhosis (AC) and alcohol-associated hepatitis (AH) being two clinical manifestations with poor prognosis. The limited efficacy of standard of care for AC and AH highlights a need for therapeutic targets and strategies. The current study aimed to address this need through the identification of hepatic proteome and phosphoproteome signatures of AC and AH. Proteomic and phosphoproteomic analyses were conducted on explant liver tissue (test cohort) and liver biopsies (validation cohort) from patients with AH. Changes in protein expression across AH severity and similarities and differences in AH and AC hepatic proteome were analyzed. Significant alterations in multiple proteins involved in various biological processes were observed in both AC and AH, including elevated expression of transcription factors involved in fibrogenesis (eg, Yes1-associated transcriptional regulator). Another finding was elevated levels of hepatic albumin (ALBU) concomitant with diminished ALBU phosphorylation, which may prevent ALBU release, leading to hypoalbuminemia. Furthermore, altered expression of proteins related to neutrophil function and chemotaxis, including elevated myeloperoxidase, cathelicidin antimicrobial peptide, complement C3, and complement C5 were observed in early AH, which declined at later stages. Finally, a loss in expression of mitochondria proteins, including enzymes responsible for the synthesis of cardiolipin was observed. The current study identified hepatic protein signatures of AC and AH as well as AH severity, which may facilitate the development of therapeutic strategies. |
| Databáze: | OpenAIRE |
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