Pre-therapy liver transcriptome landscape in Indian and French patients with severe alcoholic hepatitis and steroid responsiveness
Autor: | Saggere Muralikrishna Shasthry, Emmanuel Weiss, Richard Moreau, Shvetank Sharma, Pierre-Emmanuel Rautou, Shiv Kumar Sarin, Ashwani K. Mishra, Valérie Paradis, Christophe Junot, Pierre de la Grange, C. Sharma, Sukanta Das, Jaswinder Singh Maras, Laure Elkrief, Hélène Gilgenkrantz, S. Hussain, Sophie Lotersztajn |
---|---|
Jazyk: | angličtina |
Rok vydání: | 2017 |
Předmět: |
Adult
Male 0301 basic medicine Senescence medicine.medical_specialty Science Alcoholic hepatitis Biology Article Transcriptome 03 medical and health sciences Receptors Glucocorticoid Glucocorticoid receptor Internal medicine Ethnicity medicine Humans Progenitor cell Glucocorticoids Cell Proliferation Multidisciplinary Fatty liver Middle Aged medicine.disease 3. Good health 030104 developmental biology Endocrinology Nuclear receptor Immunology Hepatocytes Medicine Female Glucocorticoid Fatty Liver Alcoholic medicine.drug |
Zdroj: | Scientific Reports, Vol 7, Iss 1, Pp 1-9 (2017) Scientific Reports |
ISSN: | 2045-2322 |
Popis: | Patients with severe alcoholic hepatitis (SAH) not responding to glucocorticoid therapy have higher mortality, though they do not differ in their baseline clinical characteristics and prognostic scores from those who respond to therapy. We hypothesized that the baseline hepatic gene expression differs between responders (R) and non-responders (NR). Baseline liver transcriptome was compared between R and NR in Indian (16 each) and French (5 NR, 3 R) patients with SAH. There were differentially expressed genes (DEGs) between NR and R, in Indian (1106 over-expressed, 96 under-expressed genes) and French patients (65 over-expressed, 142 under-expressed genes). Indian NR had features of hepatocyte senescence and French NR exhibited under-expression of genes involved in cell division, indicating a central defect in the capacity of hepatocytes for self-renewal in both populations. Markers of hepatic progenitor cell proliferation were either very few (Indian patients) or absent (French patients). No DEGs were enriched in inflammatory pathways and there were no differences in nuclear receptor subfamily 3 group C member 1 (NR3C1) transcript expression and splicing between NR and R. Our results reveal that baseline hepatic transcriptome is reflective of subsequent glucocorticoid non-response and indicate impaired regenerative potential of the liver as an underlying phenomenon in NR. |
Databáze: | OpenAIRE |
Externí odkaz: | |
Nepřihlášeným uživatelům se plný text nezobrazuje | K zobrazení výsledku je třeba se přihlásit. |