Your browser doesn't support javascript.
loading
Distinct Hepatic Gene-Expression Patterns of NAFLD in Patients With Obesity.
Subudhi, Sonu; Drescher, Hannah K; Dichtel, Laura E; Bartsch, Lea M; Chung, Raymond T; Hutter, Matthew M; Gee, Denise W; Meireles, Ozanan R; Witkowski, Elan R; Gelrud, Louis; Masia, Ricard; Osganian, Stephanie A; Gustafson, Jenna L; Rwema, Steve; Bredella, Miriam A; Bhatia, Sangeeta N; Warren, Andrew; Miller, Karen K; Lauer, Georg M; Corey, Kathleen E.
Afiliação
  • Subudhi S; Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
  • Drescher HK; Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
  • Dichtel LE; Neuroendocrine Unit, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
  • Bartsch LM; Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
  • Chung RT; Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
  • Hutter MM; Department of Surgery, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
  • Gee DW; Department of Surgery, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
  • Meireles OR; Department of Surgery, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
  • Witkowski ER; Department of Surgery, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
  • Gelrud L; Department of Medicine, St. Mary's Hospital Bon Secours, Richmond, VA, USA.
  • Masia R; Department of Pathology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
  • Osganian SA; Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
  • Gustafson JL; Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
  • Rwema S; Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
  • Bredella MA; Division of Musculoskeletal Radiology and Interventions, Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
  • Bhatia SN; Ludwig Center for Molecular Oncology, Massachusetts Institute of Technology, Cambridge, MA, USA.
  • Warren A; Ludwig Center for Molecular Oncology, Massachusetts Institute of Technology, Cambridge, MA, USA.
  • Miller KK; Neuroendocrine Unit, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
  • Lauer GM; Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
  • Corey KE; Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
Hepatol Commun ; 6(1): 77-89, 2022 01.
Article em En | MEDLINE | ID: mdl-34558849
ABSTRACT
Approaches to manage nonalcoholic fatty liver disease (NAFLD) are limited by an incomplete understanding of disease pathogenesis. The aim of this study was to identify hepatic gene-expression patterns associated with different patterns of liver injury in a high-risk cohort of adults with obesity. Using the NanoString Technologies (Seattle, WA) nCounter assay, we quantified expression of 795 genes, hypothesized to be involved in hepatic fibrosis, inflammation, and steatosis, in liver tissue from 318 adults with obesity. Liver specimens were categorized into four distinct NAFLD phenotypes normal liver histology (NLH), steatosis only (steatosis), nonalcoholic steatohepatitis without fibrosis (NASH F0), and NASH with fibrosis stage 1-4 (NASH F1-F4). One hundred twenty-five genes were significantly increasing or decreasing as NAFLD pathology progressed. Compared with NLH, NASH F0 was characterized by increased inflammatory gene expression, such as gamma-interferon-inducible lysosomal thiol reductase (IFI30) and chemokine (C-X-C motif) ligand 9 (CXCL9), while complement and coagulation related genes, such as C9 and complement component 4 binding protein beta (C4BPB), were reduced. In the presence of NASH F1-F4, extracellular matrix degrading proteinases and profibrotic/scar deposition genes, such as collagens and transforming growth factor beta 1 (TGFB1), were simultaneously increased, suggesting a dynamic state of tissue remodeling.

Conclusion:

In adults with obesity, distinct states of NAFLD are associated with intrahepatic perturbations in genes related to inflammation, complement and coagulation pathways, and tissue remodeling. These data provide insights into the dynamic pathogenesis of NAFLD in high-risk individuals.
Assuntos
Texto completo
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Expressão Gênica / Hepatopatia Gordurosa não Alcoólica / Obesidade Tipo de estudo: Etiology_studies / Prognostic_studies / Risk_factors_studies Limite: Adult / Female / Humans / Male / Middle aged Idioma: En Revista: Hepatol Commun Ano de publicação: 2022 Tipo de documento: Article País de afiliação: Estados Unidos
Texto completo
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Expressão Gênica / Hepatopatia Gordurosa não Alcoólica / Obesidade Tipo de estudo: Etiology_studies / Prognostic_studies / Risk_factors_studies Limite: Adult / Female / Humans / Male / Middle aged Idioma: En Revista: Hepatol Commun Ano de publicação: 2022 Tipo de documento: Article País de afiliação: Estados Unidos