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| Status |
Public on Oct 26, 2017 |
| Title |
Investigating the effect of NIK SMI1, a small molecule inhibitor of NIK, on TWEAK-stimulated Mouse renal proximal tubule-interstitial epithelial cells (RPTEC) |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Systemic lupus erythematosus (SLE) is often considered a disease driven by autoreactive B cells and anti-nuclear antibodies. However, therapeutic targeting of B cells, for example through BAFF blockade, has been only partially effective in SLE. NF-κB Inducing Kinase (NIK) mediates non-canonical NF-κB signaling downstream of disease relevant TNF family members, such as BAFF, TWEAK, CD40, and OX40. We hypothesized that NIK inhibition might be more efficacious than BAFF blockade in lupus, and therefore generated highly selective and potent small molecule inhibitors (SMI) of NIK to test this hypothesis. RNASeq was used to investigate the effects of one of these SMIs of NIK, NIK SMI1, on TWEAK-stimulated Mouse renal proximal tubule-interstitial epithelial cells (RPTEC).
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| Overall design |
To address the role of NIK in renal TWEAK signaling, we focused on renal proximal tubulo-interstitial epithelial cells (RPTEC), as this cell type is highly relevant to the well described pro-inflammatory role TWEAK plays in the kidney. Mouse RPTEC were cultured as suggested by commercial source. 5x10^6 cells were stimulated with recombinant mouse TWEAK (100 ng/mL, R&D Systems) for 6 and 24 hours in the presence or absence of NIK SMI1 (~IC90 = 3 µM) or vehicle (DMSO) with 3 replicates per treatment. Extracted RNA was analyzed by RNASeq
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| Contributor(s) |
Brightbill HD, Suto E, Blaquiere N, Ramamoorthi N, SujathaBhaskar S, Gogol E, Castanedo G, Jackson B, Haller S, Lesch J, Bents K, Everett C, Kohli PB, Linge S, Christian L, Barrett K, Jaochico A, Berezhkovskiy LM, Fan PW, Veliz K, Townsend M, DeVoss J, Johnson A, Godemann R, Lee WP, Austin CD, McKenzie B, Hackney JA, Crawford JJ, Staben S, Ismaili MH, Wu LC, Ghilardi N |
| Citation(s) |
29330524 |
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| Submission date |
Oct 26, 2016 |
| Last update date |
Mar 08, 2021 |
| Contact name |
Mark McCreary |
| E-mail(s) |
mccrearm@gene.com
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| Phone |
6502254332
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| Organization name |
Genentech
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| Department |
Bioinformatics
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| Street address |
1 DNA Way, MS 93
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| City |
South San Francisco |
| State/province |
California |
| ZIP/Postal code |
94080 |
| Country |
USA |
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| Platforms (1) |
| GPL13112 |
Illumina HiSeq 2000 (Mus musculus) |
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| Samples (18)
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| Relations |
| BioProject |
PRJNA350616 |
| SRA |
SRP092094 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE89195_RAW.tar |
7.2 Mb |
(http)(custom) |
TAR (of TAB) |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
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