A Comparative Kidney Transcriptome Analysis of Bicarbonate-Loaded insrr-Null Mice

Gantsova, E. A.; Serova, O. V.; Eladari, D.; Bobrovskiy, D. M.; Petrenko, A. G.; Elchaninov, A. V.; Deyev, I. E.

doi:10.3390/cimb45120606

Cited by 1 publication

(1 citation statement)

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“…Interestingly, Insrr can be activated by alkaline pH and is required for normal response to an alkaline diet in rodents 42 . Recent transcriptomic analysis of Insrr-null mouse kidneys revealed decreased expression of pendrin along with differential expression of genes associated with ATP metabolism and electron transport chain 43 , suggestive that Insrr modulates metabolism to maintain type B ICs in a mature functional state. Although our study clearly identifies Irs1 as directly repressed by Hes1 in PCs, it remains to be determined if up regulation of Irs1 in PCs is sufficient to drive them towards an IC state.…”

Section: Discussionmentioning

confidence: 99%

Kidney collecting duct cell type composition is regulated by Notch signaling via modulation of mTORC1

deRiso,

Mukherjee,

Janga

et al. 2024

Preprint

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The plasticity and diversity of cell types with specialized functions likely defines the capacity of multicellular organisms to adapt to physiologic stressors. The kidney collecting ducts contribute to water, electrolyte, and pH homeostasis and are composed of mature intermingled epithelial cell types that are susceptible to transdifferentiate. The conversion of kidney collecting duct principal cells to intercalated cells is actively inhibited by Notch signaling to ensure urine concentrating capability. Here we identify Hes1, a target of Notch signaling, allows for maintenance of functionally distinct epithelial cell types within the same microenvironment by regulating mechanistic target of rapamycin complex 1 (mTORC1) activity. Hes1 directly represses the expression ofinsulin receptor substrate 1(Irs1), an upstream component of mTOR pathway and suppresses mTORC1 activity in principal cells. Genetic inactivation oftuberous sclerosis complex 2(Tsc2) to increase mTORC1 activity in mature principal cells is sufficient to promote acquisition of intercalated cell properties, while inhibition of mTORC1 in adult kidney epithelia suppresses intercalated cell properties. Considering that mTORC1 integrates environmental cues, the linkage of functionally distinct epithelial cell types to mTORC1 activity levels likely allows for cell plasticity to be regulated by physiologic and metabolic signals and the ability to sense/transduce these signals.

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Section: Discussionmentioning

confidence: 99%