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Role of WNT10A-expressing kidney fibroblasts in acute interstitial nephritis.

ABSTRACT: WNT signaling mediates various physiological and pathological processes. We previously showed that WNT10A is a novel angio/stromagenic factor involved in such processes as tumor growth, wound healing and tissue fibrosis. In this study, we investigated the role of WNT10A in promoting the fibrosis that is central to the pathology of acute interstitial nephritis (AIN). We initially asked whether there is an association between kidney function (estimated glomerular filtration rate; eGFR) and WNT10A expression using kidney biopsies from 20 patients with AIN. Interestingly, patients with WNT10A expression had significantly lower eGFR than WNT10A-negative patients. However, changes in kidney function were not related to the level of expression of other WNT family members. Furthermore, there was positive correlation between WNT10A and ?-SMA expression. We next investigated the involvement of WNT10A in kidney fibrosis processes using COS1 cells, a kidney fibroblast cell line. WNT10A overexpression increased the level of expression of fibronectin and peroxiredoxin 5. Furthermore, WNT10A overexpression renders cells resistant to apoptosis induced by hydrogen peroxide and high glucose. Collectively, WNT10A may induce kidney fibrosis and associate with kidney dysfunction in AIN.

SUBMITTER: Kuma A

PROVIDER: S-EPMC4108433 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

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Role of WNT10A-expressing kidney fibroblasts in acute interstitial nephritis.

Kuma Akihiro A Yamada Sohsuke S Wang Ke-Yong KY Kitamura Noriaki N Yamaguchi Takahiro T Iwai Yoshiko Y Izumi Hiroto H Tamura Masahito M Otsuji Yutaka Y Kohno Kimitoshi K

PloS one 20140723 7

WNT signaling mediates various physiological and pathological processes. We previously showed that WNT10A is a novel angio/stromagenic factor involved in such processes as tumor growth, wound healing and tissue fibrosis. In this study, we investigated the role of WNT10A in promoting the fibrosis that is central to the pathology of acute interstitial nephritis (AIN). We initially asked whether there is an association between kidney function (estimated glomerular filtration rate; eGFR) and WNT10A ...[more]

PMID: 25054240

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Project description:BackgroundAcute interstitial nephritis (AIN) is an important and common cause of acute renal failure. There are no generally accepted guidelines for the treatment of AIN, due to the lack of prospective randomized trials. Since AIN is characterized by an enhanced immune response, immunosuppressive treatment could potentially improve prognosis by attenuating inflammation and subsequent fibrosis. Despite the limited evidence of effects of steroids and potential adverse effects, prednisolone is frequently used in the treatment of AIN and there is a strong need for clinical trials on the effects of immunosuppression, including steroids, in the treatment of AIN. We aimed to evaluate the effectiveness of prednisolone treatment in AIN, and hypothesized a positive effect of prednisolone treatment on renal function in AIN.MethodsThe study is a randomized, controlled, prospective, open label multicenter study, including incident adult patients with biopsy proven AIN. Patients will be randomized 1:1 to one of 2 treatment regimens: A. No prednisolone treatment (control group) and B. B) Oral prednisolone treatment staring with 60 mg daily tapered over 8 weeks. One hundred ten patients (55 in each group) are planned to be included and followed for 1 year. Primary outcome is renal function estimated by eGFR 3 months after inclusion. Secondary outcomes are renal function after 12 months and need for renal replacement therapy and quality of life after 3 and 12 months. In addition, with-in prednisolone group analysis are performed to estimate the importance of treatment delay. Exploratory analyses include analysis of biomarkers in urine and plasma and the evaluation of these biomarkers in relation to renal prognosis and re-evaluation of renal biopsies to identify possible renal prognostic factors.DiscussionStrengths and possible limitations in the design are evaluated. The study will provide important information on the effects of prednisolone treatment in AIN and as well as prognostic information relevant for future use of biomarkers and histology. Ultimately, this would lead to improved and evidence based clinical guidelines for the treatment of AIN.Trial registrationClinicalTrials.gov identifier NCT04376216 (Retrospectively registered on May 6, 2020).

Dataset Information

Role of WNT10A-expressing kidney fibroblasts in acute interstitial nephritis.

Publications

Role of WNT10A-expressing kidney fibroblasts in acute interstitial nephritis.

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