The tubulogenic effect of aldosterone is attributed to intact binding and intracellular response of the mineralocorticoid receptor |
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Authors: | Will W Minuth Lucia Denk Kanghong Hu Hayo Castrop Celso Gomez-Sanchez |
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Institution: | (1) Department of Molecular and Cellular Anatomy, University of Regensburg, D-93053 Regensburg, Germany;(2) Institute of Physiology, University of Regensburg, D-93053 Regensburg, Germany;(3) Division of Endocrinology, G.V. (Sonny) Montgomery VA Medical Center and University of Mississippi Medical Center, Jackson, Mississippi, 39216, USA |
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Abstract: | Little is known about the extra- and intracellular stimuli inducing renal stem/progenitor cells to develop into three-dimensionally
structured tubules. To study this specific development in a controlled environment, we used an advanced culture technique.
Embryonic tissue derived from neonatal rabbit kidney was placed in a perfusion culture container at the interface of an artificial
interstitium made of a polyester fleece. Culture was carried out in chemically defined Iscove’s Modified Dulbecco’s Medium
(IMDM) for 13 days. Development of tubules was histochemically detected on cryosections labeled with Soybean Agglutinin (SBA).
The experiments showed that aldosterone exerts a specific tubulogenic effect. Application of aldosterone (1 × 10−7 M) raised numerous SBA-labeled tubules, while in the absence of the steroid hormone the development of tubules was lacking.
Specificity of hormone action was analyzed by the use of aldosterone antagonists. Administration of spironolactone (1 × 10−4 M) and canrenoate (1 × 10−5 M) completely inhibited the development of tubules. Finally, disrupting the intracellular molecular complex of the mineralocorticoid
receptor (MR) and heat shock proteins by geldanamycin (2 μg/ml) prevented the development of tubules. Our results suggest that the tubulogenic effect induced by aldosterone is attributed
to both hormone binding and an undisturbed intracellular response of the MR. |
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Keywords: | Stem/progenitor cells aldosterone mineralocorticoid receptor perfusion culture artificial interstitium kidney |
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