| Objective: Signaling by the WNT family is one of the fundamental mechanisms thatdirect cell differentiation, cell proliferation, cell polarity and cell fate determinationthrough autocrine/paracrine during embryonic development and tissue homeostasis.Recent studies have confirmed that WNT/β-catenin signaling appeared important innormal wound healing and its sustaining activation was associated with fibrogenesis. Thecanonical WNT pathway was identified as a factor in the pathogenesis of a variety ofkidney disease. In NZB/NZW mice model,WNT signaling pathway may related in thepathogenesis of lupus nephritis.This study aimed to evaluate WNT. signaling activity inlupus nephritis, and to explore the potential role of WNT pathway in the pathogenesis oflupus nephritis.Methods: β-catenin expression was assayed in the kidneys of88lupus nephritis patientsand15normal kidney tissue by immunohistochemical methods. The expression ofmessenger RNA(mRNA) in the kidney of64lupus nephritis patients and34normalkidney tissue for β-catenin, Axin2and Dickkopf-1(DKK-1) were measured by RT-PCR.Plasma level of DKK-1was measured in50lupus nephritis and40normal control.Results: Immunohistochemistry revealed increased β-catenin in kidneys of patients withlupus nephritis compared to normal kidney tissue, paralleled by mRNA expression. Thisincrease in mRNA expression of β-catenin was higher in patients with class V comparedwith normal controls and class IV. RT-PCR analyses also revealed the mRNA expressions of β-catenin were significantly increased in patient without renal interstitial fibrosis thanthose in patient with renal interstitial fibrosis. The mRNA expression of Axin2and DKK-1increased slightly in lupus nephritis patients than those in normal control, but nosignificant changes was found. The mRNA expression of DKK-1had positive correlationwith β-catenin. Plasma levels of WNT inhibitor DKK-1in patients lupus nephritis weresignificantly increased compared to healthy controls.There were nagtive correlationbetween the concentration of ds-DNA and DKK-1, and positive correlation between theconcentration of C3and DKK-1.Plasma levels of DKK-1was higher in patients with classV compared with normal controls.Conclusion: In our study, the canonical WNT/β-catenin signaling activity was increasedin lupus nephritis. Altered WNT/β-catenin signaling was related to the pathogenesis oflupus nephritis. The role of WNT Pathway may be not same in different pathological typesof lupus nephritis. The over expression of β-catenin may happen before the occurrence ofinterstitial fibrosis. The role of DKK-1could be complex in SLE. Further study of WNT/β-catenin pathway would help to understand the pathogenesis of lupus nephritis, and tofind a new therapeutic target. |
