title: [Optimization and characterization of a novel FGF21 mutant].
abstract: Fibroblast growth factor 21 (FGF21) is a member of FGF family. It has been demonstrated that FGF21 is an independent, safe and effective regulator of blood glucose levels in vivo. In order to improve the activity of FGF21, we exchanged the beta10-beta12 domain of the human FGF21 with that of the mouse FGF21 to construct a novel FGF21 gene (named hmFGF21), and then subcloned hmFGF21 gene into the SUMO expression vector to create pSUMO-hmFGF21 and transformed it into E. coli Rosetta for expression of the fusion protein SUMO-hmFGF21. Both in vitro and in vivo glucose regulation activity of hmFGF21 was evaluated. The SDS-PAGE result showed that compared with wild-type hFGF21, the soluble expression of hmFGF21 increased about 2-fold. HmFGF21 was more potent in stimulation of glucose uptake in HepG2 cells in vitro. The results of anti-diabetic effect on db/db mice demonstrated that hmFGF21 had better efficacy on controlling the blood glucose of the db/db diabetic animals than wild-type hFGF21. These results suggest that the biological properties of FGF21 are significantly improved by optimization.
authors.affiliation: College of Life Science, Northeast Agricultural University, Harbin 150030, China.
authors.forename: Xian-Long
authors.initials: XL
authors.lastname: Ye
authors.forename: Hua-Shan
authors.initials: HS
authors.lastname: Gao
authors.forename: Wen-Fei
authors.initials: WF
authors.lastname: Wang
authors.forename: Gui-Ping
authors.initials: GP
authors.lastname: Ren
authors.forename: Ming-Yao
authors.initials: MY
authors.lastname: Liu
authors.forename: Kun
authors.initials: K
authors.lastname: He
authors.forename: Ya-Kun
authors.initials: YK
authors.lastname: Zhang
authors.forename: Jing-Zhuang
authors.initials: JZ
authors.lastname: Zhao
authors.forename: Dan
authors.initials: D
authors.lastname: Yu
authors.forename: De-Shan
authors.initials: DS
authors.lastname: Li
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism*; D003546:Cysteine Endopeptidases; D003921:Diabetes Mellitus, Experimental / Q000097:blood*; D010450:Endopeptidases / Q000235:genetics*; D004926:Escherichia coli; D005346:Fibroblast Growth Factors / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology; D005822:Genetic Vectors; D005947:Glucose / Q000378:metabolism; D056945:Hep G2 Cells / Q000378:metabolism; D006801:Humans; D007004:Hypoglycemic Agents / Q000378:metabolism / Q000494:pharmacology; D008297:Male; D051379:Mice; D009154:Mutation; D010957:Plasmids; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology; D014170:Transformation, Genetic
chemical_list: D001786:Blood Glucose; D007004:Hypoglycemic Agents; D011993:Recombinant Fusion Proteins; C414620:fibroblast growth factor 21; D005346:Fibroblast Growth Factors; D010450:Endopeptidases; C404512:SENP1 protein, human; D003546:Cysteine Endopeptidases; D005947:Glucose