Analysis of epithelial-mesenchymal transition (EMT) process in renal collecting ducts of aging rats

BRANDÁN, Y.R.; GUAYTIMA, E.V; FAVALE, N. O.; STERIN-SPEZIALE, N.B.; MÁRQUEZ, M. G.

Paraná, Entre Ríos

Congreso; LIV REUNIÓN ANUAL DE LA SOCIEDAD ARGENTINA DE INVESTIGACIONES EN BIOQUÍMICA Y BIOLOGÍA MOLECULAR (SAIB); 2018

SOCIEDAD ARGENTINA DE INVESTIGACIONES EN BIOQUÍMICA Y BIOLOGÍA MOLECULAR (SAIB)

Renal aging is associated with alterations in organ morphology and function. The EMT process has been suggested as a mechanism that drives fibrosis, with the consequent loss of tissue functions. In previous works, we demonstrated that inhibition of sphingomyelin synthase I (SMS1) activity induces collecting ducts (CD) cells to lose their epithelial phenotype and to undergo an EMT process. Now we investigated the occurrence of EMT in renal papilla CD cells of aging rats (6 month). Taking advantage of the fact that CD in primary cultured retain many characteristics of their behavior in intact tissue, primary cultures of CD cells from young (70 days) and aging rats were performed. We analyzed the expression of epithelial and mesenchymal (vimentin and α-smooth muscle actin, α-SMA) cells markers, cell proliferation, and the presence of primary cilia by immunocytochemistry. Contrary to what was observed in young rats, CD cells from aging rats exhibited impairment of cell-cell adhesion, a high expression of vimentin and α-SMA, and a significant increased number of isolated cells with fibroblastoid-like morphology expressing both proteins. We also observed greater proliferation and a decreased number of cells with primary cilium. These features are consistent with the alterations reported in tubular epithelial cells during renal fibrosis. The increased proliferation probably represents a mechanism to restore the integrity of the tubular epithelium. Our results suggest that as aging occurs, the balance between the EMT-MET processes in renal papilla is altered, but the link between these alterations and the lack of activity of SMS1 requires further studies.