New insights into functions, regulation, and pathological roles of tight junctions in kidney tubular epithelium

Epithelial tight junctions (TJs) seal off the intercellular space to generate a paracellular barrier as well as a selective transport pathway. They also maintain apicobasal polarization of cells. In addition, TJs serve as signaling platforms that orchestrate many epithelial functions. The past years have brought about a remarkable increase in our understanding of the structure and function of TJs. The overall aim of this review is to provide an update on this new knowledge, with special emphasis on TJs in the kidney tubular epithelium. TJs are key determinants of tubular transport processes, contributing to ion and fluid homeostasis. They are also central organizers of the structure of the tubular epithelium and many aspects of tubular cell functions, beyond transport processes. Many pathological states in the kidney, including inflammation, acute kidney injury, and chronic progressive diseases affect the tubular TJs, with important consequences with regards to the pathogenesis and pathophysiology of various nephropathies. In fact, altered TJ structure and function are increasingly recognized as a key step in the generation of renal diseases. In this review, we provide an overview of the protein composition, function and regulation of TJs in the kidney tubules, as well as their involvement and role in diseases.