| First Author | Tayyeb A | Year | 2022 |
| Journal | Cells | Volume | 11 |
| Issue | 8 | PubMed ID | 35456008 |
| Mgi Jnum | J:324180 | Mgi Id | MGI:7265425 |
| Doi | 10.3390/cells11081329 | Citation | Tayyeb A, et al. (2022) Calreticulin Shortage Results in Disturbance of Calcium Storage, Mitochondrial Disease, and Kidney Injury. Cells 11(8) |
| abstractText | Renal Ca(2+) reabsorption plays a central role in the fine-tuning of whole-body Ca(2+) homeostasis. Here, we identified calreticulin (Calr) as a missing link in Ca(2+) 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 Ca(2+) storage capacity. Consequently, the kidney cells displayed an abnormal activation of Ca(2+) signaling and NF-kappaB pathways, resulting in inflammation and wide progressive kidney injury. Interestingly, the disturbance in the Ca(2+) 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. |
