Research Article Details

Article ID: A23021
PMID: 24113587
Source: Int J Mol Sci
Title: Role of hepatic progenitor cells in nonalcoholic fatty liver disease development: cellular cross-talks and molecular networks.
Abstract: Nonalcoholic fatty liver disease (NAFLD) includes a spectrum of diseases ranging from simple fatty liver to nonalcoholic steatohepatitis, (NASH) which may progress to cirrhosis and hepatocellular carcinoma. NASH has been independently correlated with atherosclerosis progression and cardiovascular risk. NASH development is characterized by intricate interactions between resident and recruited cells that enable liver damage progression. The increasing general agreement is that the cross-talk between hepatocytes, hepatic stellate cells (HSCs) and macrophages in NAFLD has a main role in the derangement of lipid homeostasis, insulin resistance, danger recognition, immune tolerance response and fibrogenesis. Moreover, several evidences have suggested that hepatic stem/progenitor cell (HPCs) activation is a component of the adaptive response of the liver to oxidative stress in NAFLD. HPC activation determines the appearance of a ductular reaction. In NASH, ductular reaction is independently correlated with progressive portal fibrosis raising the possibility of a periportal fibrogenetic pathway for fibrogenesis that is parallel to the deposition of subsinusoidal collagen in zone 3 by HSCs. Recent evidences indicated that adipokines, a class of circulating factors, have a key role in the cross-talk among HSCs, HPCs and liver macrophages. This review will be focused on cellular cross-talk and the relative molecular networks which are at the base of NASH progression and fibrosis.
DOI: 10.3390/ijms141020112

Strategy ID Therapy Strategy Synonyms Therapy Targets Therapy Drugs
S01 Improve insulin resistance insulin sensitizer; insulin resistance; glucose tolerance Biguanide: increases 5-AMP activated protein kinase signaling; SGLT-2 inhibitor; Thiazalidinedione: selective PPAR-γ agonists; GLP-1 agonist Metformin; Empagliflozin; Canagliflozin; Rosiglitazone; Pioglitazone; Liraglutide Details
S03 Anti-fibrosis fibrosis Angiotensin Receptor Blocker (ARB); CCR2/CCR5 antagonist; Thyroid receptor β agonist; PEGylated human FGF21 analogue; Monoclonal antibody to lysyl oxidase-like 2 (LOXL2); Galectin-3 inhibitor; FGF19 variant Losartan; Cenicriviroc; VK-2809; MGL-3196; Pegbelfermin; Simtuzumab; GR-MD-02; NGM282 Details
S04 Anti-oxidative stress oxidative stress α-tocopherol: antioxidant Vitamin E Details

Target ID Target Name GENE Action Class UniProtKB ID Entry Name

Diseases ID DO ID Disease Name Definition Class
I05 9352 Type 2 diabetes mellitus A diabetes that is characterized by chronic hyperglycaemia with disturbances of carbohydrate, fat and protein metabolism resulting from defects in insulin secretion, insulin action, or both. A diabetes mellitus that is characterized by high blood sugar, insulin resistance, and relative lack of insulin. http://en.wikipedia.org/wiki/Diabetes, http://en.wikipedia.org/wiki/Diabetes_mellitus_type_2 disease of metabolism/inherited metabolic disorder/ carbohydrate metabolic disorder/glucose metabolism disease/diabetes/ diabetes mellitus Details
I07 1936 Arteriosclerosis Build-up of fatty material and calcium deposition in the arterial wall resulting in partial or complete occlusion of the arterial lumen.https://ncit.nci.nih.gov/ncitbrowser/ConceptReport.jsp?dictionary=NCI_Thesaurus&ns=ncit&code=C35768 disease of anatomical entity/cardiovascular system disease/ vascular disease/ artery disease Details

Drug ID Drug Name Type DrugBank ID Targets Category Latest Progress
D545 Pig placenta extract Biological extract -- -- -- Under clinical trials Details
D083 CLA Chemical drug DB01211 KCNH2; SLCO1B1; SLCO1B3 -- Under clinical trials Details
D182 Insulin Biological drug DB00030 INSR agonist; CPE modulator&product of -- Under clinical trials Details