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

ABSTRACT

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 perfusion container for 13 days. Development was registered with Soybean Agglutinin (SBA). Microscopy revealed that treatment with aldosterone (1 x 10-7 M) resulted in numerous SBA-labeled tubules. Interference with mineralocorticoid receptor (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 tubule development. Disturbing MR and hsp 70 with quercetin (2 x 10-4 M) and KNK 437 (1 x 10-4 M) generated SBAlabeled 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 aldosterone is mediated by interaction of MR, hsp 90, hsp 70 and immunophilin FKBP 12.

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