Altered response of pendrin-positive intercalated cells in the kidney of Hoxb7-Cre;Mib1f/f mice.

Abstract

The anion exchanger pendrin is exclusively expressed by non-type A intercalated cells (ICs), type B ICs and non A-non B ICs. Pendrin-positive ICs are mainly localized in the cortical collecting duct (CCD) and connecting tubule (CNT) rather than the outer medullary collecting duct (OMCD). Our previous study reported that Notch signaling is required for the specification of ureteric bud cells to the principal cells (PCs) and ICs in the medullary collecting duct. The purpose of this study was to determine whether the deletion of Mind bomb-1 (Mib1), an E3 ubiquitin ligase required for the initiation of Notch signaling, would affect the differentiation of pendrin-positive type B and non A-non B ICs in Hoxb7-Cre;Mib1f/f mice. In Hoxb7-Cre;Mib1f/f mice, there was a significant increase in the fraction of pendrin-negative/AE1-positive type A ICs not only in the OMCD (67.02±2.04% vs. 33.78±0.71%; Hoxb7-Cre;Mib1f/f vs. Mib1f/f) but also in the CCD (23.70±2.68% vs. 19.71±0.43%; Hoxb7-Cre;Mib1f/f vs. Mib1f/f) and CNT (23.70±2.68% vs. 19.71±0.43%; Hoxb7-Cre;Mib1f/f vs. Mib1f/f) as compared with Mib1f/f. In contrast, there were no significant differences in the fraction of pendrin-positive type B ICs (7.11±3.84% vs. 7.61±4.45%; Hoxb7-Cre;Mib1f/f vs. Mib1f/f) between the two groups in the cortex including CCD and CNT. Furthermore, there was a significant decrease in the fraction of non A-non B ICs (8.95±2.28% vs. 13.06±4.81%; Hoxb7-Cre;Mib1f/f vs. Mib1f/f) in these tubules in the Hoxb7-Cre;Mib1f/f mice. These results suggest that the degree of differentiation of subtypes of ICs may vary depending on the Notch signaling pathway.