gms | German Medical Science

Introduction: Chronic allograft nephropathy is characterized by arterial remodeling, tubular atrophy, graft fibrosis, and renal dysfunction. Its pathogenesis is poorly understood and no therapies are available. Nestin, a constituent of intermediate filaments, is a marker of progenitor cells which may contribute to chronic allograft remodeling. Here, we test the hypothesis, that Nestin is over-expressed in renal allografts during the development of chronic nephropathy.

Materials and methods: Renal transplantation was performed in the allogeneic Fischer 344 to Lewis rat strain combination. Isogeneic transplantation was done in the Lewis rat and untreated Lewis rats served as controls. Nestin-expression was investigated by real-time RT-PCR, Westernblotting and immunohistochemistry in controls and in grafts on days 9 and 42 post-transplantation (n = 4 per group).

Results: On histological sections of untreated control kidneys, Nestin-immunoreactivity was detected in all glomeruli and in very few interstitial cells. Allogeneic transplantation additionally resulted in Nestin-positve arterial endothelial cells, some parts of the tubular system, and interstitial cells. Nestin-immunoreactivity peaked on day 9 after allogeneic transplantation and slightly decreased until day 42. In contrast, in day 9 isografts, Nestin-signals were only slightly increased and returned to control levels on day 42. These immunohistochemical data were corroborated by Westernblotting. Real-time RT-PCR, however, revealed no significant changes in Nestin mRNA-expression.

Conclusion: In this study, we demonstrate that the protein concentration of Nestin increases in renal grafts in response to transplantation. This increase in Nestin-expression is transient in isografts, whereas in accordance with our hypothesis, the number of Nestin-positive cells remains elevated at least for 6 weeks in allografts which develop chronic nephropathy. As we did not observe any changes in mRNA-expression, we assume that the expression of Nestin is regulated on the post-transcriptional level. Nestin-positive progenitor cells probably contribute to allograft remodeling.