Ghrelin attenuates plasminogen activator inhibitor-1 production induced by tumor necrosis factor-alpha in HepG2 cells via NF-kappaB pathway.
Plasminogen activator inhibitor type 1 (PAI-1), produced partly from liver is a risk factor for macrovascular and microvascular complications of diabetes. Ghrelin, a recently described orexigenic peptide hormone, attenuates PAI-1 induced by TNF-alpha in the human hepatoma cell line (HepG2). Exposure to TNF-alpha (1 ng/ml) for 24h caused a significant increase in PAI-1 mRNA expression and protein secretion, as evaluated by RT-PCR and ELISA, but pretreatment with ghrelin (1-100 ng/ml) inhibited both basal and TNF-alpha-induced PAI-1 release in a dose and time-dependent manner in HepG2. PDTC, selective NF-kappaB inhibitor, had no additive inhibitory effects with ghrelin. The results indicate that ghrelin inhibits both basal and TNF-alpha-induced PAI-1 production via NF-kappaB pathway in HepG2 cells, and suggest that the peptide plays a therapeutic role in atherosclerosis, especially in obese patients with insulin resistance, in whom ghrelin levels were reduced.
Ding
Liying
L
Department of Endocrinology, First Hospital of China Medical University, ShenYang 110001, China.
Liu
Guoliang
G
Guo
Wenshi
W
Zhao
Hong
H
Zong
Zhihong
Z
D000328:Adult; D000818:Animals; D006528:Carcinoma, Hepatocellular; D045744:Cell Line, Tumor; D054439:Ghrelin / Q000494:pharmacology / Q000502:physiology*; D006801:Humans; D008113:Liver Neoplasms; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D017395:Plasminogen Activator Inhibitor 1 / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism*
D054439:Ghrelin; D016328:NF-kappa B; D017395:Plasminogen Activator Inhibitor 1; D014409:Tumor Necrosis Factor-alpha