title: Decrease of FGF receptor (FGFR) and interstitial fibrosis in the kidney of streptozotocin-induced diabetic rats.
abstract: Fibrosis is the final disorder of end-stage renal disease. Activation of fibroblast growth factor (FGF) 23-klotho axis could suppress renal fibrosis in mice. Also, a marked decrease of klotho expression was observed in the kidney of streptozotocin-induced diabetic rats (STZ rats). However, relation of FGF in renal fibrosis remained unclear. This study was aimed to screen the effect of hyperglycemia on FGF receptor (FGFR) and fibrosis in kidney of rats with diabetic nephropathy and investigate this potential mechanism in cultured Madin-Darby Canine Kidney (MDCK) epithelial cells. STZ rats were used to treat with insulin or phloridzin at the dose sufficient to correct hyperglycemia for understanding the changes of renal dysfunction. The cultured MDCK cells were also used to treat with high glucose, hydrogen peroxide, or tiron in addition to transfection of siRNA to silence the klotho. Both insulin and phloridzin reversed fibrosis and FGFR expressions in kidney of STZ rats. It was confirmed in high glucose-exposed MDCK cells. However, klotho failed to modify the level of FGFR in MDCK cells. Meanwhile, FGFR was restored by tiron in MDCK cells and in diabetic rats without changing blood glucose. In conclusion, interstitial fibrosis and decreased FGFR expression are observed in the kidney of diabetic rats. This change is reversed by tiron without the correction of blood glucose. Also, klotho has no effect on expression of FGFR. Thus, decrease of oxidative stress is useful for the recovery of FGFR expression and improvement of renal fibrosis in type-1 like diabetic rats.
authors.affiliation: Division of Nephrology, Department of Internal Medicine, National Cheng Kung University Hospital, Tainan City, Taiwan.
authors.forename: M F
authors.initials: MF
authors.lastname: Cheng
authors.affiliation: Institute of Basic Medical Science, College of Medicine, National Cheng Kung University, Tainan City, Taiwan.
authors.forename: L J
authors.initials: LJ
authors.lastname: Chen
authors.affiliation: Division of Nephrology, Department of Internal Medicine, National Cheng Kung University Hospital, Tainan City, Taiwan.
authors.forename: M C
authors.initials: MC
authors.lastname: Wang
authors.affiliation: Department of Pathology, Edah University Medical Center, Yanchao, Kaohsiung City, Taiwan.
authors.forename: C T
authors.initials: CT
authors.lastname: Hsu
authors.affiliation: Institute of Basic Medical Science, College of Medicine, National Cheng Kung University, Tainan City, Taiwan.
authors.forename: J T
authors.initials: JT
authors.lastname: Cheng
mesh_terms: D014013:1,2-Dihydroxybenzene-3,5-Disulfonic Acid Disodium Salt / Q000494:pharmacology; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000097:blood / Q000150:complications / Q000378:metabolism* / Q000473:pathology*; D003928:Diabetic Nephropathies / Q000150:complications / Q000378:metabolism / Q000473:pathology; D004285:Dogs; D000089703:Fibroblast Growth Factor-23; D005355:Fibrosis; D005966:Glucuronidase / Q000378:metabolism; D006943:Hyperglycemia / Q000150:complications / Q000378:metabolism / Q000473:pathology; D007328:Insulin / Q000494:pharmacology; D007668:Kidney / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology*; D007684:Kidney Tubules / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D000090265:Klotho Proteins; D061985:Madin Darby Canine Kidney Cells; D008297:Male; D051379:Mice; D010695:Phlorhizin / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D017468:Receptors, Fibroblast Growth Factor / Q000378:metabolism*; D013481:Superoxides / Q000378:metabolism
chemical_list: D001786:Blood Glucose; C000717428:Fgf23 protein, mouse; D007328:Insulin; D017468:Receptors, Fibroblast Growth Factor; D013481:Superoxides; D014013:1,2-Dihydroxybenzene-3,5-Disulfonic Acid Disodium Salt; D000089703:Fibroblast Growth Factor-23; D010695:Phlorhizin; D005966:Glucuronidase; D000090265:Klotho Proteins