ORAI channels are critical for receptor-mediated endocytosis of albumin.

ABSTRACT: Impaired albumin reabsorption by proximal tubular epithelial cells (PTECs) has been highlighted in diabetic nephropathy (DN), but little is known about the underlying molecular mechanisms. Here we find that ORAI1-3, are preferentially expressed in PTECs and downregulated in patients with DN. Hyperglycemia or blockade of insulin signaling reduces the expression of ORAI1-3. Inhibition of ORAI channels by BTP2 and diethylstilbestrol or silencing of ORAI expression impairs albumin uptake. Transgenic mice expressing a dominant-negative Orai1 mutant (E108Q) increases albuminuria, and in vivo injection of BTP2 exacerbates albuminuria in streptozotocin-induced and Akita diabetic mice. The albumin endocytosis is Ca²⁺-dependent and accompanied by ORAI1 internalization. Amnionless (AMN) as

SUBMITTER: Zeng B 

PROVIDER: S-EPMC5714946 | biostudies-literature | 2017 Dec

REPOSITORIES: biostudies-literature