The sclerosing glomerulus in mice and man: novel insights

Segmental glomerulosclerosis is the end-point of a series of processes with have podocyte damage as a common denominator. This review summarizes the important advances that have been made in the past 2 years leading to the comprehension of several molecular mechanisms of regulation of podocyte physiology and pathology.

From recent studies it has become clear that the dynamic cytoskeleton of podocyte foot processes has to be highly regulated to maintain cell shape and function. The importance of intracellular calcium in this process has started to be revealed, together with the channels and the organelles appointed to calcium entry and buffering.Novel data highlight the centrality and the complexity of the mammalian target of rapamycin pathways, which are implicated in the regulation of autophagy. Similarities between podocytes and neuronal cells have been extended to the process of dynamin-regulated endocytosis, and further data in mice and humans provide support to the idea that podocytes can be directly targeted by old and new drugs.

Research is bringing numerous advances regarding the role of podocytes in the development of glomerulosclerosis, which can lead to novel and specific therapeutic approaches, as well as to a more rational use of drugs already in use. Consequently, renal biopsy becomes the indispensable instrument not only for diagnosis but also to precisely detect molecular therapeutic targets and guide personalized therapy.