CiteULike: jyuh Sheikh

S100A4: a common mediator of epithelial-mesenchymal transition, fibrosis and regeneration in diseases?

Mikael Schneider — 2008-04-21T10:26:03-00:00

Journal of molecular medicine (Berlin, Germany) (6 March 2008)

Multiple reports have focused on S100A4's role in cancer progression, specifically its ability to enhance metastasis. However, recent studies have linked S100A4 to several diseases besides cancer, including kidney fibrosis, cirrhosis, pulmonary disease, cardiac hypertrophy and fibrosis, arthritis and neuronal injuries. Common to all these diseases is the involvement of fibrotic and inflammatory processes, i.e. processes greatly dependent on tissue remodelling, cell motility and epithelial-mesenchymal transition. Therefore, the basic biological mechanisms behind S100A4's effects are emerging. S100A4 belongs to the S100 family of proteins that contain two Ca(2+)-binding sites including a canonical EF-hand motif. S100A4 is involved in the regulation of a wide range of biological effects including cell motility, survival, differentiation and contractility. S100A4 has both intracellular and extracellular effects. Hence, S100A4 interacts with cytoskeletal proteins and enhances metastasis of several types of cancer cells. In addition, S100A4 is secreted by unknown mechanisms, thus, paracrinely stimulating a variety of cellular responses, including angiogenesis and neuronal growth. Although many cellular effects of S100A4 are well described, the molecular mechanisms whereby S100A4 elicits these responses remain largely unknown. However, it is likely that the intracellular and the extracellular effects involve distinct mechanisms. In this review, we explore the possible roles of S100A4 in non-cancer diseases and employ this knowledge to describe underlying biological mechanisms including a change in cellular phenotype towards less tightly adherent cells and activation of fibrotic processes that may explain this protein's involvement in multiple pathologies.

The regulation of energy generating metabolic pathways by p53.

CA Corcoran — 2007-08-31T16:16:52-00:00

Cancer Biol Ther, Vol. 5, No. 12. (December 2006), pp. 1610-1613.

The function of p53 as a tumor suppressor remains undisputed. p53 has a central role in cellular stress responses as well as affecting cancer development and progression. The word "central", however, is becoming increasingly more of an understatement as the list of p53-regulated pathways and processes is ever expanding. Although much focus continues to center on p53-mediated signaling cascades that control cell growth arrest and/or apoptosis, recent work has begun to define a role for p53 in the regulation of metabolic pathways typically thought of as essential for maintaining life. With the first potential link between p53 and glycolysis reported nearly ten years ago, the topic has gained a renewed interest. Recent studies now demonstrate the ability of p53 to regulate the expression of several novel genes including PGM (phosphoglycerate mutase), TIGAR (TP53-induced glycolysis and apoptosis regulator) and, SCO2 (synthesis of cytochrome c oxidase 2), each intimately linked to the processes of glycolysis and oxidative phosphorylation. With this discovery, yet another novel means by which p53 carries out its tumor suppressor function is brought into light.

The role of renal biopsy in women with kidney disease identified in pregnancy.

Clara Day — 2007-08-28T09:51:51-00:00

Nephrol Dial Transplant (25 August 2007)

BACKGROUND: Renal disease may present for the first time in pregnancy, either as symptomatic disease or as a consequence of antenatal screening. The role of antenatal and post-partum percutaneous renal biopsy in the management of such patients is discussed. METHODS: We describe two series of women; the first is a series of 20 women presenting with renal disease of a severity to warrant renal biopsy during pregnancy whilst the second, comprises 75 women who had an initial presentation of renal disease in pregnancy and underwent post-partum renal biopsy. RESULTS: Biopsy during pregnancy revealed a glomerular disorder in 19/20 (95%) with immediate change of management in 9/20 (40%). In 17/20 (85%) there was delivery of a live infant at median gestation of 36 weeks (range 25-40). Follow-up of women [median 103.3 months (2.5-256)] showed 9/20 (45%) had a GFR of <60 ml/min/1.73 m(2) [six at end-stage renal failure (ESRF)] and 3/20 were dead. The majority (62/75; 82.6%) of women undergoing post-partum renal biopsy presented with significant proteinuria (40% pre-eclampsia) during pregnancy not resolving post-partum. A glomerular abnormality was found in 64%. At last follow-up of 47 women [median 51.5 months (range 1-212)], 14 patients (29.7%) had significant proteinuria and 20 (42.6%) had a GFR<60 ml/min/1.73 m(2). Six women (12.7%) had ESRF. CONCLUSIONS: Diagnosis and follow-up of renal disease diagnosed in pregnancy is important as progressive disease occurs in this group. Routine antenatal screening provides a useful diagnostic opportunity to detect asymptomatic renal disease. In a selected sub-group, renal biopsy during pregnancy can be helpful in initiation of correct treatment and allowing progression of pregnancy to fetal viability.