Decrease of FGF receptor (FGFR) and interstitial fibrosis in the kidney of streptozotocin-induced diabetic rats

Horm Metab Res. 2014 Jan;46(1):1-7. doi: 10.1055/s-0033-1349090. Epub 2013 Jul 4.

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.

MeSH terms

  • 1,2-Dihydroxybenzene-3,5-Disulfonic Acid Disodium Salt / pharmacology
  • Animals
  • Blood Glucose / metabolism
  • Diabetes Mellitus, Experimental / blood
  • Diabetes Mellitus, Experimental / complications
  • Diabetes Mellitus, Experimental / metabolism*
  • Diabetes Mellitus, Experimental / pathology*
  • Diabetic Nephropathies / complications
  • Diabetic Nephropathies / metabolism
  • Diabetic Nephropathies / pathology
  • Dogs
  • Fibrosis
  • Glucuronidase / metabolism
  • Hyperglycemia / complications
  • Hyperglycemia / metabolism
  • Hyperglycemia / pathology
  • Insulin / pharmacology
  • Kidney / drug effects
  • Kidney / metabolism*
  • Kidney / pathology*
  • Kidney Tubules / drug effects
  • Kidney Tubules / metabolism
  • Kidney Tubules / pathology
  • Madin Darby Canine Kidney Cells
  • Male
  • Mice
  • Phlorhizin / pharmacology
  • Rats
  • Rats, Wistar
  • Receptors, Fibroblast Growth Factor / metabolism*
  • Superoxides / metabolism

Substances

  • Blood Glucose
  • Insulin
  • Receptors, Fibroblast Growth Factor
  • Superoxides
  • 1,2-Dihydroxybenzene-3,5-Disulfonic Acid Disodium Salt
  • Phlorhizin
  • Glucuronidase
  • klotho protein