Thiazolidinedione attenuate proteinuria and glomerulosclerosis in Adriamycin-induced nephropathy rats via slit diaphragm protection.
OBJECTIVE
The slit diaphragm (SD) of podocyte impairment contributes to massive proteinuria and progressive glomerulosclerosis in many human glomerular diseases. The aim of the study was to determine if thiazolidinedione (TZD) reduce proteinuria and glomerulosclerosis in focal segmental glomerulosclerosis (FSGS) by preserving the structure and function of SD.


METHODS
Adriamycin-induced FSGS rat models were employed. Urinary protein content was measured dynamically during the experiment. Additional biochemical parameters in serum samples were measured after the animals were killed. Glomerular sclerosis index (SI) and podocyte foot processes fusion rate (PFR) were evaluated. The protein and mRNA expressing levels of nephrin, podocin and CD2-associated protein (CD2AP) in glomeruli were assessed by immunohistochemistry and real-time quantitative polymerase chain reaction, respectively. The density of podocytes was also evaluated after anti-Wilms' tumour-1 immunohistochemical staining.


RESULTS
Rosiglitazone treatment partially reduced proteinuria, but did not significantly affect the serum levels of triglyceride, cholesterol, albumin, glucose, urea nitrogen and creatinine in Adriamycin-induced FSGS rats. Glomerular SI and podocyte foot PFR were significantly attenuated by rosiglitazone treatment. Rosiglitazone prevented the reduction of nephrin, podocin and CD2AP protein expression induced by Adriamycin, however, the mRNA expression levels of these SD-related markers did not change significantly. Rosiglitazone therapy did not reverse Adriamycin-mediated reduction of the density of podocytes.


CONCLUSIONS
The study data suggest that TZD are promising therapeutic agents on FSGS, and the mechanism may be mediated in part by directly protecting the structure and function of SD.
Liu
Hua-Feng
HF
Institute of Nephrology, Guangdong Medical College, Zhanjiang, Guangdong, China. hf-liu@263.net
Guo
Li-Qin
LQ
Huang
Yu-Ying
YY
Chen
Keng
K
Tao
Jing-Li
JL
Li
Shang-Mei
SM
Chen
Xiao-Wen
XW
D000818:Animals; D004317:Doxorubicin / Q000008:administration & dosage; D005923:Glomerulosclerosis, Focal Segmental / Q000517:prevention & control*; D007674:Kidney Diseases / Q000139:chemically induced / Q000150:complications; D008297:Male; D050199:Podocytes / Q000187:drug effects; D011507:Proteinuria / Q000517:prevention & control*; D051381:Rats; D017207:Rats, Sprague-Dawley; D045162:Thiazolidinediones / Q000627:therapeutic use*
D045162:Thiazolidinediones; D004317:Doxorubicin; C089946:2,4-thiazolidinedione