Aberrant activation of the WNT/β-catenin signaling pathway in lupus nephritis.
OBJECTIVE
The canonical WNT pathway has been implicated as playing important roles in the pathogenesis of a variety of kidney diseases. Recently, WNT pathway activity was reported to be elevated in the renal tissue of a lupus mouse model. This study aimed to evaluate the potential role of the WNT pathway in the pathogenesis of human lupus nephritis.


METHODS
The expression of β-catenin was evaluated in renal biopsy specimens from lupus nephritis patients and control kidney tissues by immunohistochemistry and western blotting. Real-time polymerase chain reaction (RT-PCR) was used to detect RNA expression of β-catenin, Dkk-1 and Axin2. Plasma concentrations of Dkk-1 were measured by ELISA.


RESULTS
Immunohistochemistry and western blotting revealed increased expression of β-catenin in the kidneys of patients with lupus nephritis compared with control kidney tissues (p<0.05), accompanied by an increase in mRNA expression of β-catenin (p<0.01) and axin2 (p<0.05). β-catenin was significantly greater in LN patients without renal interstitial fibrosis compared with those with renal interstitial fibrosis (p<0.01) at the mRNA expression level; the increase in β-catenin mRNA positively correlated with the creatinine clearance rate (Ccr) and negatively correlated with chronicity indices of renal tissue injury. Greater plasma Dkk-1 concentrations were found in LN patients compared with controls (p<0.05). Plasma Dkk-1 concentrations also correlated negatively with anti-dsDNA antibody levels and positively with serum C3 levels.


CONCLUSIONS
The canonical WNT/β-catenin signaling pathway was activated in lupus nephritis patients, accompanied by an increase in plasma levels of Dkk-1. Altered WNT/β-catenin signaling was related to the pathogenesis of lupus nephritis and might play a role in renal fibrosis.
Department of Rheumatology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University Shanghai Institute of Rheumatology, Shanghai, PR China.
Xiao-Dong
XD
Wang
Department of Rheumatology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University Shanghai Institute of Rheumatology, Shanghai, PR China.
Xin-Fang
XF
Huang
Department of Rheumatology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University Shanghai Institute of Rheumatology, Shanghai, PR China.
Qing-Ran
QR
Yan
Department of Rheumatology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University Shanghai Institute of Rheumatology, Shanghai, PR China.
Chun-de
CD
Bao
D000328:Adult; D000974:Antibodies, Antinuclear / Q000097:blood; D060466:Axin Protein / Q000235:genetics / Q000378:metabolism; D016022:Case-Control Studies; D003176:Complement C3 / Q000378:metabolism; D003404:Creatinine / Q000097:blood; D005260:Female; D005355:Fibrosis; D015870:Gene Expression; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000097:blood / Q000235:genetics; D007668:Kidney / Q000378:metabolism / Q000473:pathology; D007677:Kidney Function Tests; D008181:Lupus Nephritis / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D012333:RNA, Messenger / Q000235:genetics* / Q000378:metabolism; D060449:Wnt Signaling Pathway / Q000235:genetics*; D051176:beta Catenin / Q000235:genetics / Q000378:metabolism
C491761:AXIN2 protein, human; D000974:Antibodies, Antinuclear; D060466:Axin Protein; C495270:CTNNB1 protein, human; D003176:Complement C3; C501126:DKK1 protein, human; D036341:Intercellular Signaling Peptides and Proteins; D012333:RNA, Messenger; D051176:beta Catenin; D003404:Creatinine