|
| Status |
Public on Jul 08, 2024 |
| Title |
Insulin receptor deletion in kidney intercalated cells suppresses collecting duct immune defenses |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
|
| Summary |
Urinary tract infection (UTI) significantly impacts people with diabetes mellitus. Insulin resistance, the primary abnormality leading to Type 2 diabetes, is defined by inefficient insulin receptor signaling. In the kidney, insulin receptor deletion in intercalated cells increases UTI susceptibility. Here, we use RNA sequencing to profile the transcriptomes of enriched intercalated cell and neighboring principal cell populations from mice with intercalated cell-specific insulin receptor deletion and compare expression profiles to wild-type mice. We also establish unique intercalated cell and principal cell cultures to assess the functional impact of insulin receptor deletion. Transcriptomic analysis and culture models demonstrate intercalated cells with insulin receptor deletion are more susceptible to uropathogenic Escherichia coli infection and have suppressed integrated stress responses. They also show the integrated stress response is necessary to activate NFkB-mediated immune responses. When NFkB is silenced, intercalated cells do not activate innate immune responses, including the production of antimicrobial peptides, which increases infection susceptibility.
|
| |
|
| Overall design |
Comparative gene expression profiling analysis of RNA-seq data for FACS enriched intercalated cells and principal cells from IR floxed control mice and Atp6v1b1-Cre/IRKO mice.
|
| Web link |
https://pubmed.ncbi.nlm.nih.gov/38976738/
|
| |
|
| Contributor(s) |
Spencer JD, Schwartz LL |
| Citation(s) |
38976738 |
| |
| Submission date |
Sep 22, 2022 |
| Last update date |
Oct 08, 2024 |
| Contact name |
John David Spencer |
| Organization name |
Nationwide Children's Hospital
|
| Street address |
700 Children's Drive
|
| City |
Columbus |
| State/province |
OH |
| ZIP/Postal code |
43205 |
| Country |
USA |
| |
|
| Platforms (1) |
| GPL21103 |
Illumina HiSeq 4000 (Mus musculus) |
|
| Samples (16)
|
|
| Relations |
| BioProject |
PRJNA883415 |
Less...
More...