Academic Journal
Interferon Regulatory Factor‐5 in Resident Macrophage Promotes Polycystic Kidney Disease
| العنوان: | Interferon Regulatory Factor‐5 in Resident Macrophage Promotes Polycystic Kidney Disease |
|---|---|
| المؤلفون: | Zimmerman, Kurt A., Huang, Jifeng, He, Lan, Revell, Dustin Z., Li, Zhang, Hsu, Jung-Shan, Fitzgibbon, Wayne R., Hazard, E. Starr, Hardiman, Gary, Mrug, Michal, Bell, P. Darwin, Yoder, Bradley K., Saigusa, Takamitsu |
| المساهمون: | HHS | NIH | National Institute of Diabetes and Digestive and Kidney Diseases, PKD Foundation, U.S. Department of Veterans Affairs, HHS | National Institutes of Health, UAB | School of Medicine, University of Alabama at Birmingham |
| المصدر: | Kidney360 ; volume 1, issue 3, page 179-190 ; ISSN 2641-7650 |
| بيانات النشر: | Ovid Technologies (Wolters Kluwer Health) |
| سنة النشر: | 2020 |
| الوصف: | Background Autosomal dominant polycystic kidney disease is caused by genetic mutations in PKD1 or PKD2 . Macrophages and their associated inflammatory cytokines promote cyst progression; however, transcription factors within macrophages that control cytokine production and cystic disease are unknown. Methods In these studies, we used conditional Pkd1 mice to test the hypothesis that macrophage-localized interferon regulatory factor-5 (IRF5), a transcription factor associated with production of cyst-promoting cytokines (TNF α , IL-6), is required for accelerated cyst progression in a unilateral nephrectomy (1K) model. Analyses of quantitative real-time PCR (qRT-PCR) and flow-cytometry data 3 weeks post nephrectomy, a time point before the onset of severe cystogenesis, indicate an accumulation of inflammatory infiltrating and resident macrophages in 1K Pkd1 mice compared with controls. qRT-PCR data from FACS cells at this time demonstrate that macrophages from 1K Pkd1 mice have increased expression of Irf5 compared with controls. To determine the importance of macrophage-localized Irf5 in cyst progression, we injected scrambled or IRF5 antisense oligonucleotide (ASO) in 1K Pkd1 mice and analyzed the effect on macrophage numbers, cytokine production, and renal cystogenesis 6 weeks post nephrectomy. Results Analyses of qRT-PCR and IRF5 ASO treatment significantly reduced macrophage numbers, Irf5 expression in resident—but not infiltrating—macrophages, and the severity of cystic disease. In addition, IRF5 ASO treatment in 1K Pkd1 mice reduced Il6 expression in resident macrophages, which was correlated with reduced STAT3 phosphorylation and downstream p-STAT3 target gene expression. Conclusions These data suggest that Irf5 promotes inflammatory cytokine production in resident macrophages resulting in accelerated cystogenesis. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| DOI: | 10.34067/kid.0001052019 |
| DOI: | 10.34067/KID.0001052019 |
| الاتاحة: | http://dx.doi.org/10.34067/kid.0001052019 https://journals.lww.com/10.34067/KID.0001052019 |
| رقم الانضمام: | edsbas.C497605A |
| قاعدة البيانات: | BASE |
| DOI: | 10.34067/kid.0001052019 |
|---|