title: Loss of FGF21 in diabetic mouse during hepatocellular carcinogenetic transformation.
abstract: Diabetes associated metabolic syndrome has been shown to be an independent risk factor for the development of hepatocellular carcinoma (HCC). Cirrhosis, in fact, was not always a prerequisite of HCC development and this might particularly apply to the metabolic abnormality associated HCC. This study was to investigate diabetes associated HCC and the potential role of FGF21 during carcinogenetic transformation of HCC. Dimethylnitrosamine (DEN) was used to induce HCC in the diabetic OVE26 mice. Pronounced damage characterized by steatohepatitis was found in the liver of diabetic mice. Steatohepatitis accompanied by constant cell proliferation and tumor cell growth were also found in the hepatic tissues of diabetic OVE26 mice when DEN being administrated. FGF21 protein level increased in liver tissues at an early stage along with steatohepatitis in diabetic OVE26 mice, but decreased in liver tissues later when HCC was developed. In addition, decreased FGF21 protein level was associated with cancerous hyper-proliferation and aberrant p53 and TGF-β/Smad signaling during HCC development. Loss of FGF21 may play an important role in HCC carcinogenetic transformation during metabolic liver injury in diabetic animals. The present finding calls attention to the need to control metabolic disorders associated with diabetes and may further develop a protective strategy against HCC.
authors.affiliation: Department of Infectious Diseases, Affiliated Hospital of Guiyang Medical College Guiyang, Guizhou 550004, China ; Chinese-American Research Institute for Diabetic Complications Ruian Center, The Department of Endocrinology, The Third Affiliated Hospital of Wenzhou Medical University Ruian, Zhejiang 325200, China.
authors.forename: Quan
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: Department of Surgery, School of Medicine, University of Louisville Louisville, KY 40202, USA.
authors.forename: Yan
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Infectious Diseases, Affiliated Hospital of Guiyang Medical College Guiyang, Guizhou 550004, China ; Chinese-American Research Institute for Diabetic Complications Ruian Center, The Department of Endocrinology, The Third Affiliated Hospital of Wenzhou Medical University Ruian, Zhejiang 325200, China.
authors.forename: Tingting
authors.initials: T
authors.lastname: Liang
authors.affiliation: Chinese-American Research Institute for Diabetic Complications Ruian Center, The Department of Endocrinology, The Third Affiliated Hospital of Wenzhou Medical University Ruian, Zhejiang 325200, China.
authors.forename: Xuemian
authors.initials: X
authors.lastname: Lu
authors.affiliation: The First Hospital of Jilin University Changchun 130021, China.
authors.forename: Xingkai
authors.initials: X
authors.lastname: Liu
authors.affiliation: Chinese-American Research Institute for Diabetic Complications Ruian Center, The Department of Endocrinology, The Third Affiliated Hospital of Wenzhou Medical University Ruian, Zhejiang 325200, China.
authors.forename: Chi
authors.initials: C
authors.lastname: Zhang
authors.affiliation: The First Hospital of Jilin University Changchun 130021, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Jiang
authors.affiliation: Department of Surgery, School of Medicine, University of Louisville Louisville, KY 40202, USA.
authors.forename: Robert C
authors.initials: RC
authors.lastname: Martin
authors.affiliation: Department of Infectious Diseases, Affiliated Hospital of Guiyang Medical College Guiyang, Guizhou 550004, China.
authors.forename: Mingliang
authors.initials: M
authors.lastname: Cheng
authors.affiliation: Chinese-American Research Institute for Diabetic Complications Ruian Center, The Department of Endocrinology, The Third Affiliated Hospital of Wenzhou Medical University Ruian, Zhejiang 325200, China ; Kosair Children's Hospital Research Institute, The Department of Pediatrics of The University of Louisville Louisville, KY 40202.
authors.forename: Lu
authors.initials: L
authors.lastname: Cai
keywords: FGF21; Hepatocellular carcinoma; OVE26 mice; diabetes; dimethylnitrosamine