Abstract
Gas1 (Growth Arrest-Specific 1) is a pleiotropic protein with novel functions including anti-proliferative and proapoptotic activities. In the kidney, the expression of Gas1 has been described in mesangial cells. In this study, we described that renal parietal cells of Bowman’s capsule (BC) and the distal nephron cells also express Gas1. The role of Gas1 in the kidney is not yet known. There is a subpopulation of progenitor cells in Bowman’s capsule with self-renewal properties which can eventually differentiate into podocytes as a possible mechanism of regeneration in the early stages of diabetic nephropathy. We analyzed the expression of Gas1 in the parietal cells of Bowman’s capsule in murine experimental diabetes. We found that diabetes reduced the expression of Gas1 and increased the expression of progenitor markers like NCAM, CD24, and SIX1/2, and mesenchymal markers like PAX2 in the Bowman’s capsule. We also analyzed the expression of WT1 (a podocyte-specific marker) on BC and observed an increase in the number of WT1 positive cells in diabetes. In contrast, nephrin, another podocyte-specific protein, decreases its expression in the first week of diabetes in the glomerular tuft, which is gradually restored during the second and third weeks of diabetes. These results suggest that in diabetes the decrease of Gas1 promotes the activation of parietal progenitor cells of Bowman’s capsule that might differentiate into podocytes and compensate their loss observed in this pathology.
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Acknowledgements
The authors are very grateful to staff of UPEAL-Cinvestav, MVZ. Benjamín Emmanuel Chávez Álvarez, MVZ. Rafael Leyva-Muñoz, MVZ. Ma. Antonieta López-López, for their support in the care of laboratory animals. The authors acknowledge the technical assistance of Pablo Benito Bautista MD, PhD and José Javier Reyes-Lagos PhD. The authors acknowledge financial support by Consejo Nacional de Ciencia y Tecnología (CONACyT) to Brenda I. Luna-Anotnio (Grant 514913) and J.S. (Grant 239516).
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418_2017_1550_MOESM1_ESM.tif
Supplementary Figure 1: Expression of Gas1 in the glomerulus. a Gas1 immunofluorescence, we observed that in the glomerular tuft there is expression of Gas1(red) in control rats but in the first week of diabetes the expression decreased and it is restored in the second and third weeks of diabetes. b We observed a similar expression of Gas1 when we analyzed by ELISA isolated glomeruli. Scale bar, 50 µm. Its shown Gas1 (red) and DAPI (blue). White dotted lines delimit glomerulus. Values are means ± standard deviation (SD). n=3, ***p<0.001, ****p<0.0001. We used as positive control NIH 3T3 cells with serum starvation. (TIF 217 KB)
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Luna-Antonio, B.I., Rodriguez-Muñoz, R., Namorado-Tonix, C. et al. Gas1 expression in parietal cells of Bowman’s capsule in experimental diabetic nephropathy. Histochem Cell Biol 148, 33–47 (2017). https://doi.org/10.1007/s00418-017-1550-z
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DOI: https://doi.org/10.1007/s00418-017-1550-z