Calpastatin prevents Angiotensin II–mediated podocyte injury through maintenance of autophagy

Abstract

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Enhanced Orai1-mediated store-operated Ca2+ channel/calpain signaling contributes to high glucose-induced podocyte injury

“…Calpains are intracellular Ca 2+ -activated cysteine proteases, which are mainly activated by increased intracellular Ca 2+ (23). Activation of calpain signaling was recently demonstrated to mediate Ang II-induced podocyte injury (49). Podocytes possess multiple Ca 2+ entry pathways and different Ca 2+ signals may have distinct downstream effectors.…”

“…One advantage of sharing the same effector among different Ca 2+ pathways is that the Ca 2+ signals from different sources converge on one molecule where all signals are integrated to a final message delivered to next event. Because podocyte injury in many kidney diseases results from overloading intracellular Ca 2+ due to abnormal activation of various Ca 2+ channels and inhibition on calpain, the common effector of different Ca 2+ signaling pathways may be a therapeutic option, as suggested by a recent study (49).…”

BaoShenTongLuo formula protects against podocyte injury by regulating AMPK-mediated mitochondrial biogenesis in diabetic kidney disease.

“…Therefore, we assume that these active compounds may be involved in the podocyte protection effect of BSTL by improving mitochondrial dysfunction in DKD. Podocytes that are exposed to hyperglycaemia often undergo a variety of pathological changes, including hypertrophy, dedifferentiation, foot process effacement, detachment, loss, and apoptosis, thus resulting in proteinuria and glomerulosclerosis, which are representative features of DKD (29)(30)(31)(32). Of note, podocyte damage often occurs in the early stage of DKD (33).…”

Endothelial Autophagy Dysregulation in Diabetes

“…Furthermore, links between angiotensin signaling and autophagy exist in non-ECs [ 168 , 169 , 170 , 171 ]. Notably, the mechanisms of autophagy regulation by the angiotensin system imply mTOR, AMPK [ 172 ], and calpains [ 173 ].…”