Hepatic senescence marker protein-30 is involved in the progression of nonalcoholic fatty liver disease

作者：Park Hyohun; Ishigami Akihito; Shima Toshihide; Mizuno Masayuki; Maruyama Naoki; Yamaguchi Kanji; Mitsuyoshi Hironori; Minami Masahito; Yasui Kohichiroh; Itoh Yoshito; Yoshikawa Toshikazu; Fukui Michiaki; Hasegawa Goji; Nakamura Naoto; Ohta Mitsuhiro; Obayashi Hiroshi; Okanoue Takeshi^*

来源：Journal of Gastroenterology, 2010, 45(4): 426-434.

DOI：10.1007/s00535-009-0154-3

• SMP30
• NAFLD
• NASH
• Insulin resistance
• Oxidative stress

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) a parts per thousand currency sign 2 (n = 18), NAS of 3-4 (n = 14), and NAS a parts per thousand yen 5 (n = 66).
Patients with NAS a parts per thousand yen 5 had significantly lower hepatic SMP30 levels (12.5 +/- A 8.4 ng/mg protein) than patients with NAS a parts per thousand currency sign 2 (30.5 +/- A 14.2 ng/mg protein) and patients with NAS = 3-4 (24.6 +/- A 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 a parts per thousand yen 5 were significantly higher than those seen in patients with NAS a parts per thousand currency sign 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.

• 出版日期2010-4