 |
 |
GEO help: Mouse over screen elements for information. |
|
| Status |
Public on May 07, 2021 |
| Title |
Receptor-mediated mitophagy regulates EPO production and protects against renal anemia |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
|
| Summary |
Erythropoietin (EPO) drives erythropoiesis and is secreted mainly by the kidney upon hypoxic or anemic stress. The paucity of EPO production in renal EPO-producing cells (REPs) causes renal anemia, one of the most common complications of chronic nephropathies. Although mitochondrial dysfunction is commonly observed in several renal and hematopoietic disorders, the mechanism by which mitochondrial quality control impacts renal anemia remains elusive. In this study, we showed that FUNDC1, a mitophagy receptor, plays a critical role in EPO-driven erythropoiesis induced by stresses. Mechanistically, EPO production is impaired in REPs in Fundc1-/- mice upon stresses, and the impairment is caused by the accumulation of damaged mitochondria, which consequently leads to the elevation of the reactive oxygen species (ROS) level and triggers inflammatory responses by up-regulating proinflammatory cytokines. These inflammatory factors promote the myofibroblastic transformation of REPs, resulting in the reduction of EPO production. We therefore provide a link between aberrant mitophagy and deficient EPO generation in renal anemia. Our results also suggest that the mitochondrial quality control safeguards REPs under stresses, which may serve as a potential therapeutic strategy for the treatment of renal anemia.
|
| |
|
| Overall design |
Here, we performed RNA-seq of R2 erythrocytes from Fundc1 deficient mouses and WT to further study the molecular changed between KO and WT.
|
| |
|
| Contributor(s) |
Geng G, Liu J, Xu C, Chen Q, Zhu Y, Shi L |
| Citation(s) |
33942716 |
| |
| Submission date |
Sep 22, 2020 |
| Last update date |
May 10, 2021 |
| Contact name |
Changlu Xu |
| E-mail(s) |
xuchanglu@ihcams.ac.cn
|
| Organization name |
Chinese Academy of Medical Sciences & Peking Union Medical College
|
| Department |
State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Institute of Hematology & Blood Diseases Hospital
|
| Street address |
288 Nanjing Rd, Heping
|
| City |
TianJin |
| State/province |
TianJin |
| ZIP/Postal code |
300020 |
| Country |
China |
| |
|
| Platforms (1) |
| GPL13112 |
Illumina HiSeq 2000 (Mus musculus) |
|
| Samples (6)
|
|
| Relations |
| BioProject |
PRJNA664995 |
| SRA |
SRP284911 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE158361_Fundc1_ko_wt_fpkm_filtered.txt.gz |
627.2 Kb |
(ftp)(http) |
TXT |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data are available on Series record |
|
|
|
|
 |
Less...
More...