Research Article Details

Article ID: A26691
PMID: 19946731
Source: J Gastroenterol
Title: Hepatic senescence marker protein-30 is involved in the progression of nonalcoholic fatty liver disease.
Abstract: BACKGROUND: Both insulin resistance and increased oxidative stress in the liver are associated with the pathogenesis of nonalcoholic fatty liver disease (NAFLD). Senescence marker protein-30 (SMP30) was initially identified as a novel protein in the rat liver, and acts as an antioxidant and antiapoptotic protein. Our aim was to determine whether hepatic SMP30 levels are associated with the development and progression of NAFLD. METHODS: Liver biopsies and blood samples were obtained from patients with an NAFLD activity score (NAS) < or = 2 (n = 18), NAS of 3-4 (n = 14), and NAS > or = 5 (n = 66). RESULTS: Patients with NAS > or = 5 had significantly lower hepatic SMP30 levels (12.5 +/- 8.4 ng/mg protein) than patients with NAS < or = 2 (30.5 +/- 14.2 ng/mg protein) and patients with NAS = 3-4 (24.6 +/- 12.2 ng/mg protein). Hepatic SMP30 decreased in a fibrosis stage-dependent manner. Hepatic SMP30 levels were correlated positively with the platelet count (r = 0.291) and negatively with the homeostasis model assessment of insulin resistance (r = -0.298), the net electronegative charge modified-low-density lipoprotein (r = -0.442), and type IV collagen 7S (r = -0.350). The immunostaining intensity levels of 4-hydroxynonenal in the liver were significantly and inversely correlated with hepatic SMP30 levels. Both serum large very low-density lipoprotein (VLDL) and very small low-density lipoprotein (LDL) levels in patients with NAS > or = 5 were significantly higher than those seen in patients with NAS < or = 2, and these lipoprotein fractions were significantly and inversely correlated with hepatic SMP30. CONCLUSION: These results suggest that hepatic SMP30 is closely associated with the pathogenesis of NAFLD, although it is not known whether decreased hepatic SMP30 is a result or a cause of cirrhosis.
DOI: 10.1007/s00535-009-0154-3

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

Drug ID Drug Name Type DrugBank ID Targets Category Latest Progress
D328 Serine Chemical drug DB00133 SRR Improve insulin resistance Under clinical trials Details
D316 S-adenosyl-L-methionine Chemical drug DB00118 GNMT cofactor Antiviral Under clinical trials Details
D182 Insulin Biological drug DB00030 INSR agonist; CPE modulator&product of -- Under clinical trials Details
D055 Calcium Chemical drug DB01373 CAST; COMP; CP; BMP4; MGP -- Under clinical trials Details