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Calreticulin Shortage Results in Disturbance of Calcium Storage, Mitochondrial Disease, and Kidney Injury

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...

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Detalles Bibliográficos
Autores principales: Tayyeb, Asima, Dihazi, Gry H., Tampe, Björn, Zeisberg, Michael, Tampe, Desiree, Hakroush, Samy, Bührig, Charlotte, Frese, Jenny, Serin, Nazli, Eltoweissy, Marwa, Müller, Gerhard A., Dihazi, Hassan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9025518/
https://www.ncbi.nlm.nih.gov/pubmed/35456008
http://dx.doi.org/10.3390/cells11081329
Descripción
Sumario: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-κB 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.