Intrarenal expression of miRNAs in patients with hypertensive nephrosclerosis.
BACKGROUND
MicroRNAs (miRNAs) are non-coding, single-stranded RNA molecules that play important roles in a number of physiological and pathological processes. Previous studies showed that miRNAs targeting transcription factors ZEB1 and ZEB2 may repress epithelial-mesenchymal transition (EMT).


METHODS
We studied 34 consecutive patients with biopsy-proven hypertensive nephrosclerosis. Intrarenal expression of miR-200 family, miR-205, and miR-192 were determined. We also studied normal renal tissue from 20 patients with nephrectomy for kidney cancer as controls.


RESULTS
The level of intrarenal of miR-200a, miR-200b, miR-141, miR-429, miR-205, and miR-192 were significantly higher in patients with hypertensive nephrosclerosis than controls. Proteinuria correlated with intrarenal expression of miR-200a (r = 0.594, P < 0.001), miR-200b (r = 0.395, P = 0.004), miR-141 (r = 0.377, P = 0.007), miR-429 (r = 0.346, P = 0.013), miR-205 (r = 0.636, P < 0.001), and miR-192 (r = 0.306, P = 0.029). Estimated glomerular filtration rate (GFR) correlated with intrarenal expression of miR-200a (r = -0.374, P = 0.007) and miR-205 (r = -0.400, P = 0.005). Intrarenal expression of ZEB1 inversely correlated with intrarenal expression of miR-429, whereas expression of ZEB2 inversely correlated with miR-200a, miR-200b, and miR-429.


CONCLUSIONS
The results show that intrarenal expression of miR-200a, miR-200b, miR-141, miR-429, miR-205, and miR-192 were increased in hypertensive nephrosclerosis, and the degree of upregulation correlated with disease severity. The results suggested that these miRNA species may play important roles in the pathogenesis of hypertensive nephrosclerosis.
Wang
Gang
G
Department of Medicine and Therapeutics, Prince of Wales Hospital, The Chinese University of Hong Kong, Sha Tin, Hong Kong.
Kwan
Bonnie Ching-Ha
BC
Lai
Fernand Mac-Moune
FM
Choi
Paul Cheung-Lung
PC
Chow
Kai-Ming
KM
Li
Philip Kam-Tao
PK
Szeto
Cheuk-Chun
CC
D000328:Adult; D000368:Aged; D001794:Blood Pressure; D005260:Female; D005919:Glomerular Filtration Rate; D018398:Homeodomain Proteins / Q000378:metabolism; D006801:Humans; D006973:Hypertension / Q000150:complications* / Q000503:physiopathology; D007668:Kidney / Q000378:metabolism*; D008297:Male; D035683:MicroRNAs / Q000378:metabolism*; D008875:Middle Aged; D009400:Nephrosclerosis / Q000209:etiology* / Q000235:genetics* / Q000503:physiopathology; D012097:Repressor Proteins / Q000378:metabolism; D012720:Severity of Illness Index; D014157:Transcription Factors / Q000378:metabolism; D015854:Up-Regulation; D000074165:Zinc Finger E-box Binding Homeobox 2; D000071799:Zinc Finger E-box-Binding Homeobox 1
D018398:Homeodomain Proteins; D035683:MicroRNAs; D012097:Repressor Proteins; D014157:Transcription Factors; C486307:ZEB1 protein, human; C492363:ZEB2 protein, human; D000074165:Zinc Finger E-box Binding Homeobox 2; D000071799:Zinc Finger E-box-Binding Homeobox 1