| Autor: |
Asima Tayyeb, Gry H. Dihazi, Björn Tampe, Michael Zeisberg, Desiree Tampe, Samy Hakroush, Charlotte Bührig, Jenny Frese, Nazli Serin, Marwa Eltoweissy, Gerhard A. Müller, Hassan Dihazi |
| Jazyk: |
angličtina |
| Rok vydání: |
2022 |
| Předmět: |
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| Zdroj: |
Cells; Volume 11; Issue 8; Pages: 1329 |
| ISSN: |
2073-4409 |
| DOI: |
10.3390/cells11081329 |
| Popis: |
Renal Ca2+ reabsorption plays a central role in the fine-tuning of whole-body Ca2+ homeostasis. Here, we identified calreticulin (Calr) as a missing link in Ca2+ handling in the kidney and showed that a shortage of Calr results in mitochondrial disease and kidney pathogenesis. We demonstrated that Calr+/− mice displayed a chronic physiological low level of Calr and that this was associated with progressive renal injury manifested in glomerulosclerosis and tubulointerstitial damage. We found that Calr+/− kidney cells suffer from a disturbance in functionally active calcium stores and decrease in Ca2+ storage capacity. Consequently, the kidney cells displayed an abnormal activation of Ca2+ signaling and NF-κB pathways, resulting in inflammation and wide progressive kidney injury. Interestingly, the disturbance in the Ca2+ homeostasis and signaling in Calr+/− kidney mice cells triggered severe mitochondrial disease and aberrant mitophagy, resulting in a high level of oxidative stress and energy shortage. These findings provide novel mechanistic insight into the role of Calr in kidney calcium handling, function, and pathogenesis. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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