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Aldosterone exhibits a tubulogenic activity on renal stem/progenitor cells. Little information is available about the signaling between the mineralocorticoid receptor (MR) and the proteins in the cytoplasm. To obtain information, renal stem/progenitor cells from neonatal rabbit were cultured at the interface of an artificial polyester interstitium in a perfu- sion container for 13 days. Development was registered with Soybean Agglutinin (SBA). Microscopy revealed that treat- ment with aldosterone (1 x 10-7 M) resulted in numerous SBA-labeled tubules. Interference with mineralocorticoid recep- tor (MR) and heat shock protein (hsp) 90 using geldanamycin (3,6 x 10-6 M) or radicicol (1 x 10-6 M) showed a lack of tu- bule development. Disturbing MR and hsp 70 with quercetin (2 x 10-4 M) and KNK 437 (1 x 10-4 M) generated SBA- labeled cell cluster but not structured tubules. Interference with MR and immunophilins by cyclosporin A (2 x 10-6 M) and rapamycin (2,2 x 10-9 M) did not influence the generation of numerous SBA-labeled tubules. In contrast, administration of FK 506 (2 x 10-8 M) resulted in a lack of tubule development. Thus, the signal for development of tubules induced by al- dosterone is mediated by interaction of MR, hsp 90, hsp 70 and immunophilin FKBP 12.

Mineralocorticoid Receptor, Heat Shock Proteins and Immunophilins Participate in the Transmission of the Tubulogenic Signal of Aldosterone