Manganese promotes intracellular accumulation of AQP2 via modulating F-actin polymerization and reduces urinary concentration in mice.

Aquaporin-2 (AQP2) is a water channel protein expressed in principal cells (PCs) of the kidney collecting ducts (CDs) and plays a critical role in mediating water reabsorption and urine concentration. AQP2 undergoes both regulated trafficking mediated by vasopressin (VP) and constitutive recycling, which is independent of VP. For both pathways, actin cytoskeletal dynamics is a key determinant of AQP2 trafficking.

Re-characterization of the Glomerulopathy in CD2AP Deficient Mice by High-Resolution Helium Ion Scanning Microscopy.

Helium ion scanning microscopy (HIM) is a novel technology that directly visualizes the cell surface ultrastructure without surface coating. Despite its very high resolution, it has not been applied extensively to study biological or pathology samples. Here we report the application of this powerful technology to examine the three-dimensional ultrastructural characteristics of proteinuric glomerulopathy in mice with CD2-associated protein (CD2AP) deficiency.

Deletion of β1-integrin in collecting duct principal cells leads to tubular injury and renal medullary fibrosis.

The renal collecting duct (CD) contains two major cell types, intercalated (ICs) and principal cells (PCs). A previous report showed that deletion of β1-integrin in the entire renal CD causes defective CD morphogenesis resulting in kidney dysfunction. However, subsequent deletion of β1-integrin specifically in ICs and PCs, respectively, did not cause any morphological defects in the CDs.

ILK and cytoskeletal architecture: an important determinant of AQP2 recycling and subsequent entry into the exocytotic pathway.

Within the past decade tremendous efforts have been made to understand the mechanism behind aquaporin-2 (AQP2) water channel trafficking and recycling, to open a path toward effective diabetes insipidus therapeutics. A recent study has shown that integrin-linked kinase (ILK) conditional-knockdown mice developed polyuria along with decreased AQP2 expression. To understand whether ILK also regulates AQP2 trafficking in kidney tubular cells, we performed in vitro analysis using LLCPK1 cells stably expressing rat AQP2 (LLC-AQP2 cells).

Polarized Trafficking of AQP2 Revealed in Three Dimensional Epithelial Culture.

In renal collecting duct (CD) principal cells (PCs), vasopressin (VP) acts through its receptor, V2R, to increase intracellular cAMP leading to phosphorylation and apical membrane accumulation of the water channel aquaporin 2 (AQP2). The trafficking and function of basolaterally located AQP2 is, however, poorly understood. Here we report the successful application of a 3-dimensional Madin-Darby canine kidney (MDCK) epithelial model to study polarized AQP2 trafficking.

The roles of αV integrins in lens EMT and posterior capsular opacification.

Posterior capsular opacification (PCO) is the major complication arising after cataract treatment. PCO occurs when the lens epithelial cells remaining following surgery (LCs) undergo a wound healing response producing a mixture of α-smooth muscle actin (α-SMA)-expressing myofibroblasts and lens fibre cells, which impair vision. Prior investigations have proposed that integrins play a central role in PCO and we found that, in a mouse fibre cell removal model of cataract surgery, expression of αV integrin and its interacting β-subunits β1, β5, β6, β8 are up-regulated concomitant with α-SMA in LCs following surgery.

aV integrins and TGF-β-induced EMT: a circle of regulation.

Transforming growth factor-β (TGF-β) has roles in embryonic development, the prevention of inappropriate inflammation and tumour suppression. However, TGF-β signalling also regulates pathological epithelial-to-mesenchymal transition (EMT), inducing or progressing a number of diseases ranging from inflammatory disorders, to fibrosis and cancer. However, TGF-β signalling does not proceed linearly but rather induces a complex network of cascades that mutually influence each other and cross-talk with other pathways to successfully induce EMT.