Hepatic senescence marker protein-30 is involved in the progression of nonalcoholic fatty liver disease
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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.
Liver biopsies and blood samples were obtained from patients with an NAFLD activity score (NAS) ≤ 2 (n = 18), NAS of 3–4 (n = 14), and NAS ≥ 5 (n = 66).
Patients with NAS ≥ 5 had significantly lower hepatic SMP30 levels (12.5 ± 8.4 ng/mg protein) than patients with NAS ≤ 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 ≥ 5 were significantly higher than those seen in patients with NAS ≤ 2, and these lipoprotein fractions were significantly and inversely correlated with hepatic SMP30.
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.
KeywordsSMP30 NAFLD NASH Insulin resistance Oxidative stress
This study was supported by a Grant-in-Aid for Scientific Research (C) from the Japan Society for the Promotion of Science (Goji Hasegawa), and a Grant-in-Aid from the Ministry of Health, Labour and Welfare (Takeshi Okanoue).
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