PUBLICATION

BDNF: mRNA expression in urine cells of patients with chronic kidney disease and its role in kidney function

Authors
Endlich, N., Lange, T., Kuhn, J., Klemm, P., Kotb, A.M., Siegerist, F., Kindt, F., Lindenmeyer, M.T., Cohen, C.D., Kuss, A.W., Nath, N., Rettig, R., Lendeckel, U., Zimmermann, U., Amann, K., Stracke, S., Endlich, K.
ID
ZDB-PUB-180823-5
Date
2018
Source
Journal of Cellular and Molecular Medicine   22(11): 5265-5277 (Journal)
Registered Authors
Keywords
BDNF, CKD, biomarker, diabetes, podocyte
MeSH Terms
  • Aged
  • Animals
  • Brain-Derived Neurotrophic Factor/genetics*
  • Brain-Derived Neurotrophic Factor/urine
  • Diabetic Nephropathies/genetics*
  • Diabetic Nephropathies/pathology
  • Disease Models, Animal
  • Female
  • Gene Expression Regulation/genetics
  • Hepatitis A Virus Cellular Receptor 1/genetics*
  • Humans
  • Kidney/metabolism
  • Kidney/pathology
  • Kidney Glomerulus/metabolism
  • Kidney Glomerulus/pathology
  • Male
  • Membrane Glycoproteins/genetics*
  • Membrane Glycoproteins/urine
  • Middle Aged
  • Podocytes/metabolism
  • Podocytes/pathology
  • Proteinuria/genetics
  • Proteinuria/pathology
  • RNA, Messenger/genetics
  • Receptor, trkB/genetics*
  • Receptor, trkB/urine
  • Renal Insufficiency, Chronic/genetics*
  • Renal Insufficiency, Chronic/pathology
  • Renal Insufficiency, Chronic/urine
  • Zebrafish/genetics
PubMed
30133147 Full text @ J. Cell. Mol. Med.
Abstract
Podocyte loss and changes to the complex morphology are major causes of chronic kidney disease (CKD). As the incidence is continuously increasing over the last decades without sufficient treatment, it is important to find predicting biomarkers. Therefore, we measured urinary mRNA levels of podocyte genes NPHS1, NPHS2, PODXL and BDNF, KIM-1, CTSL by qRT-PCR of 120 CKD patients. We showed a strong correlation between BDNF and the kidney injury marker KIM-1, which were also correlated with NPHS1, suggesting podocytes as a contributing source. In human biopsies, BDNF was localized in the cell body and major processes of podocytes. In glomeruli of diabetic nephropathy patients, we found a strong BDNF signal in the remaining podocytes. An inhibition of the BDNF receptor TrkB resulted in enhanced podocyte dedifferentiation. The knockdown of the orthologue resulted in pericardial oedema formation and lowered viability of zebrafish larvae. We found an enlarged Bowman's space, dilated glomerular capillaries, podocyte loss and an impaired glomerular filtration. We demonstrated that BDNF is essential for glomerular development, morphology and function and the expression of BDNF and KIM-1 is highly correlated in urine cells of CKD patients. Therefore, BDNF mRNA in urine cells could serve as a potential CKD biomarker.
Genes / Markers
Figures
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Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping