Table of Contents

Volume 8, Issue 1

  January/February/March 2012

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ORGANOGENESIS FORUM

Lecture: New light on the role of claudins in the kidney

Jianghui Hou
Abstract | Full Text | PDF

The physiology of paracellular permeation of ions and solutes in the kidney is pivotally important but poorly understood. Claudins are the key components of the paracellular pathway. Defects in claudin function result in a broad range of renal diseases, including hypomagnesemia, hypercalciuria and nephrolithiasis. This review describes recent findings on the physiological function of claudins underlying paracellular transport mechanisms with a focus on renal Ca²⁺ handling. We have uncovered a molecular mechanism underlying paracellular Ca²⁺ transport in the thick ascending limb of Henle (TAL) that involves the functional interplay of three important claudin genes: claudin-14, 16 and 19, all of which are associated with human kidney diseases with hypercalciuria, nephrolithiasis and bone mineral loss. The Ca²⁺ sensing receptor (CaSR) signaling in the kidney has long been a mystery. By analyzing small non-coding RNA molecules in the kidney, we have uncovered a novel microRNA based signaling pathway downstream of CaSR that directly regulates claudin-14 gene expression and establishes the claudin-14 molecule as a key regulator for renal Ca²⁺ homeostasis. The molecular cascade of CaSR-microRNAs-claudins forms a regulatory loop to maintain proper Ca²⁺ homeostasis in the kidney.




REVIEWS

Development of the kidney medulla

Renfang Song and Ihor V. Yosypiv
Abstract | Full Text | PDF

The mature renal medulla, the inner part of the kidney, consists of the medullary collecting ducts, loops of Henle, vasa recta and the interstitium. The unique spatial arrangement of these components is essential for the regulation of urine concentration and other specialized kidney functions. Thus, the proper and timely assembly of medulla constituents is a crucial morphogenetic event leading to the formation of a functioning metanephric kidney. Mechanisms that direct renal medulla formation are poorly understood. This review describes the current understanding of the key molecular and cellular mechanisms underlying morphological aspects of medulla formation. Given that hypoplasia of the renal medulla is a common manifestation of congenital obstructive nephropathy and other types of congenital anomalies of the kidney and urinary tract (CAKUT), better understanding of how disruptions in medulla formation are linked to CAKUT will enable improved diagnosis, treatment and prevention of CAKUT and their associated morbidity.

A novel improved therapy strategy for diabetic nephropathy: Targeting AGEs

Xuemei Zhou, Bochu Wang, Liancai Zhu and Shilei Hao
Abstract | Full Text | PDF

Diabetic nephropathy (DN), is a disorder that causes significant morbidity and mortality. Studies on the pathological mechanisms of DN reveal that advanced glycation end products (AGEs) play an important role in the pathogenesis of DN through interacting with receptors for advanced glycation end products (RAGE), which activate a series of intracellular signaling pathways. AGEs and RAGE have therefore been considered to be two potential key targets. Although multiple studies have been made for anti-DN therapy against AGEs or RAGE, the results have been disappointing due to poor effectiveness or to side effects in clinical practice. In this hypothesis article, we propose a novel treatment based on a dual-target approach. A kind of multi-functional intelligent nanoparticle is constructed, which has a core-shell nanoparticle structure to load the dual-target drugs (AGEs inhibitors and RAGE inhibitors), and has a functional ‘RAGE analog’ to be used as ‘bait’ to catch AGEs and target them to the kidney. Owing to its advantages of having a dual-target, synergistic effect and high efficiency, the proposition may have potential applications in DN therapy.

Open Access Article

In-lab three-dimensional printing: An inexpensive tool for experimentation and visualization for the field of organogenesis

Roland Partridge, Noel Conlisk and Jamie A. Davies
Abstract | Full Text

The development of the microscope in 1590 by Zacharias Janssenby and Hans Lippershey gave the world a new way of visualizing details of morphogenesis and development. More recent improvements in this technology including confocal microscopy, scanning electron microscopy (SEM) and Optical Projection Tomography (OPT) have enhanced the quality of the resultant image. These technologies also allow a representation to be made of a developing tissue’s three-dimensional (3-D) form. With all these techniques however, the image is delivered on a flat two-dimensional (2-D) screen. 3-D printing represents an exciting potential to reproduce the image not simply on a flat screen, but in a physical, palpable three-dimensional structure. Here we explore the scope that this holds for exploring and interacting with the structure of a developing organ in an entirely novel way. As well as being useful for visualization, 3-D printers are capable of rapidly and cost-effectively producing custom-made structures for use within the laboratory. We here describe the advantages of producing hardware for a tissue culture system using an inexpensive in-lab printer.