Open AccessBDNF : mRNA expression in urine cells of patients with chronic kidney disease and its role in kidney function
Author(s) -
Endlich Nicole,
Lange Tim,
Kuhn Jana,
Klemm Paul,
Kotb Ahmed M.,
Siegerist Florian,
Kindt Frances,
Lindenmeyer Maja T.,
Cohen Clemens D.,
Kuss Andreas W.,
Nath Neetika,
Rettig Rainer,
Lendeckel Uwe,
Zimmermann Uwe,
Amann Kerstin,
Stracke Sylvia,
Endlich Karlhans
Publication year - 2018
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/jcmm.13762
Subject(s) - podocyte , diabetic nephropathy , kidney disease , renal function , medicine , endocrinology , gene knockdown , kidney , biology , proteinuria , cell culture , genetics
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.