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Lim1, an Embryonal Transcription Factor, Is Absent in Multicystic Renal Dysplasia, but Reactivated in NephroblastomasGuertl B.a · Senanayake U.a · Nusshold E.a · Leuschner I.c · Mannweiler S.a · Ebner B.b · Hoefler G.a
aInstitute of Pathology and bCentre of Medical Research, Medical University of Graz, Graz, Austria; cKiel Paediatric Tumor Registry, Department of Paediatric Pathology, University of Kiel, Kiel, Germany Corresponding Author
Barbara Guertl, MD
Institute of Pathology, Medical University of Graz
AT–8036 Graz (Austria)
Tel. +43 316 385 81397, E-Mail firstname.lastname@example.org
Objective:Lim1 (Lim homeobox 1) plays an important role during rodent renal development; however, its rolein human kidney development and disease is still unclear. Methods: We investigated LIM1 expression during human renal development, in dysplastic kidneys and in renal neoplasms using immunohistochemistry. RNA levels in renal carcinomas were determined by quantitative RT-PCR, and the potential roles of LIM1 in mesenchymal-epithelial transition and cell cycle were investigated in a cell culture model. Results: LIM1 was detected in pretubular aggregates, S-shaped and comma-shaped bodies as well as immature glomeruli between 10 and 30 weeks of gestation. Eleven dysplastic kidneys showed no expression of LIM1. In contrast, 12 of 32 nephroblastomas showed nuclear positivity. One regressive nephroblastoma had diffuse expression of LIM1 in tubular structures, all others showed focal positivity in mesenchymal, blastemal and epithelial structures. Renal cell carcinomas revealed no expression of LIM1. Overexpression of LIM1 in a cell culture model led to an increase in KERATIN7 expression but no change in the cell cycle. Conclusion: Our study supports the concept of a causative role of LIM1 deficiency in the development of multicystic kidney. In a small subset of nephroblastomas with a more diffuse expression pattern LIM1 might also contribute to the pathogenesis of these lesions.
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