Involvement of connective tissue growth factor in human and experimental hypertensive nephrosclerosis.
OBJECTIVE
Connective tissue growth factor (CTGF; CCN2) has been implicated as a marker and mediator of fibrosis in human and experimental renal disease.


METHODS
We performed a comparative analysis of CTGF expression in hypertensive patients with and without nephrosclerosis, and in uninephrectomized and sham-operated spontaneously hypertensive rats (UNX-SHR and 2K-SHR).


RESULTS
Urinary and plasma CTGF were elevated in patients with hypertensive nephrosclerosis, and increased renal CTGF expression was mainly localized in podocytes. Accordingly, elevation of urinary, plasma, and tissue CTGF in UNX-SHR coincided and correlated with proteinuria, glomerulosclerosis, and tubulointerstitial fibrosis. Thirty-two weeks after uninephrectomy, mean glomerular CTGF mRNA expression was increased 1.3-fold over baseline, mainly due to 1.7-fold higher expression in glomeruli undergoing sclerosis. In parallel, tubulointerstitial CTGF and α-smooth muscle actin were upregulated in UNX-SHR. CTGF was increased in the media of arcuate and interlobar arteries, while arterioles remained negative.


CONCLUSIONS
Glomerulosclerosis, tubulointerstitial fibrosis, and arterial media hypertrophy lesions of hypertensive nephrosclerosis are all characterized by increased CTGF tissue expression, which is associated with a concomitant increase in CTGF in blood and urine. These findings identify CTGF as a promising biomarker for progression of hypertensive nephrosclerosis, and as a likely key factor in the pathogenesis of this disease.
Ito
Yasuhiko
Y
Department of Pathology, Academic Medical Center, Amsterdam, The Netherlands.
Aten
Jan
J
Nguyen
Tri Q
TQ
Joles
Jaap A
JA
Matsuo
Seiichi
S
Weening
Jan J
JJ
Goldschmeding
Roel
R
D000328:Adult; D000368:Aged; D000818:Animals; D055513:Connective Tissue Growth Factor / Q000096:biosynthesis* / Q000097:blood / Q000652:urine; D005260:Female; D005923:Glomerulosclerosis, Focal Segmental / Q000473:pathology; D006801:Humans; D006973:Hypertension / Q000378:metabolism*; D007150:Immunohistochemistry; D007668:Kidney / Q000473:pathology / Q000502:physiology; D008297:Male; D008875:Middle Aged; D009392:Nephrectomy; D009400:Nephrosclerosis / Q000378:metabolism* / Q000473:pathology; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D011918:Rats, Inbred SHR; D053773:Transforming Growth Factor beta1 / Q000378:metabolism
D012333:RNA, Messenger; D053773:Transforming Growth Factor beta1; D055513:Connective Tissue Growth Factor