Affiliations: Department of Medicine & Therapeutics, Prince
of Wales Hospital, The Chinese University of Hong Kong, Shatin, Hong Kong, China | Department of Anatomical & Cellular Pathology,
Prince of Wales Hospital, The Chinese University of Hong Kong, Shatin, Hong Kong, China
Note: [] Corresponding auhtor: Dr. C.-C. Szeto, Department of Medicine
& Therapeutics, Prince of Wales Hospital, The Chinese University of Hong
Kong, Shatin, NT, Hong Kong, China. Tel.: +852 2632 3126; Fax: +852 2637 3852;
E-mail: [email protected]
Abstract: Background: Micro-RNAs (miRNAs) regulate one-third of all
protein-coding genes and are fundamental in the pathophysiology of a wide range
of diseases. We studied the expression of several miRNA species (miR-200
family, miR-205 and miR-192) in the urinary sediment of patients with IgA
nephropathy (IgAN). Methods: We studied 43 patients with biopsy-proven
IgAN. Urinary expression of miRNAs was determined and compared to that from 13
healthy controls. Results: The levels of urinary miR-200a, miR-200b and
miR-429, but not miR-200c, miR-141, miR-205, or miR-192, were down-regulated in
patients with IgAN. Proteinuria significantly correlated with urinary
expression of miR-200a (r= −0.483, P < 0.001), miR-200b (r= −0.448,
P=0.001) and miR-429 (r=−0.466, P=0.001). Baseline renal function
significantly correlated with urinary expression of miR-200b (r= 0.512, P
< 0.001) and miR-429 (r=0.425, P=0.005). Urinary gene expression of
ZEB2 inversely correlated with miR-200b (r=−0.321, P=0.017); and
vimentin expression inversely correlated with that of miR-200a (r=−0.360,
P=0.007), miR-200b (r=−0.416, $P =$ 0.002) and miR-429 (r=−0.375,
P=0.005). After 33.4 ± 12.6 months, the rate of renal function decline
significantly correlated with urinary expression of miR-200b (r=0.316, P=0.034). Conclusions: Urinary expression of miR-200a, miR-200b and
miR-429 were down-regulated in patients with IgAN, and the degree of reduction
correlated with disease severity and rate of progression. The results suggested
that these miRNA species might play important roles in the pathophysiology of
IgAN. Further studies are needed to clarify the role of urinary miRNA
repression as a non-invasive marker of IgAN.
