The Tumor Gene Survivin Is Highly Expressed in Adult Renal Tubular Cells

Abstract

The inhibitor of apoptosis protein survivin is of critical importance for regulation of cellular division and survival. Published data point to a restricted function of survivin in embryonic development and cancer; thus survivin has been broadly proposed as an ideal molecular target for specific anti-cancer therapy. In contrast to this paradigm, we report here broad expression of survivin in adult differentiated tissues, as demonstrated at the mRNA and protein levels. Focusing on the kidney, survivin is strongly expressed in proximal tubuli, particularly at the apical membrane, which can be verified in rat, mouse, and human kidneys. In the latter, survivin expression seems to be even stronger in proximal tubuli than in adjacent cancerous tissue. Primary and immortalized human renal tubular cells also showed high levels of survivin protein expression, and RNA interference resulted in a partial G 2 /M arrest of the cell cycle and increased rate of apoptosis. In conclusion, survivin may be of importance for renal pathophysiology and pathology The kidney is an organ with a multitude of highly specific tasks, such as maintenance of water and electrolyte homeostasis, blood pressure control, and regulation of erythropoiesis. For most of these, the tubular system is of crucial importance. Renal tubular cells are very sensitive to a large number of clinically relevant stresses, such as hypoxia/ischemia, sepsis, or different toxic agents. The uniform pathomorphological appearance of such lesions is acute tubular necrosis, which leads to acute renal failure and has profound socio-economical impact, as well as high relevance for mortality of the critically ill patients. In addition, acute tubular injury can contribute to the progression of chronic kidney disease. 1Together with the thick ascending limb of Henle, the proximal tubule is the most sensitive region of the tubular system. Most of the transepithelial transport takes place in the proximal tubule, leading to a very high rate of energy consumption. At the same time the availability of energy substrates is restricted, because tubular cells are not able to perform glycolysis and the peritubular blood supply is easily hampered because of its postcapillary character.2,3 Taken together, the proximal tubule is a functionally important but highly susceptible structure. Considering the delicate nature of the proximal tubulus, its extraordinary ability for repair is remarkable, which involves a high rate of proliferation and differentiation processes potentially leading to complete restoration of

Immunohistochemical Detection of Survivin in Canine Lymphoma

“…The finding of survivin expression in epithelia of the placenta, gastrointestinal tract and skin are in agreement with multiple immunohistochemical studies of adult human and 29 rodent tissues (Chiodino et al, 1999;Gianani et al, 2001;Ding et al, 2006;Lechler et al, 2007;Piras et al, 2007) and with expression data available from a publicly accessible repository (http://www.proteinatlas.org/). Positive expression in several further organs including testis, kidney, liver and brain ( Kobayashi et al, 1999;Altura et al, 2003;Moon and Tarnawski, 2003;Lechler et al, 2007) is supported by at least one previous study with human tissues and by data from the protein atlas.…”

“…Positive expression in several further organs including testis, kidney, liver and brain ( Kobayashi et al, 1999;Altura et al, 2003;Moon and Tarnawski, 2003;Lechler et al, 2007) is supported by at least one previous study with human tissues and by data from the protein atlas. One study in particular has demonstrated, with different methods, high survivin levels in the adult renal proximal tubules (Lechler et al, 2007 (Fukuda and Pelus, 2006) were not included in the present study but these tissues from dogs might also express survivin. In the present study, a more extensive identification of cell types was not possible in the tissue microarrays due to the limited amount of tissue examined and the limited number of tissues included.…”

“…Reports of the expression of this protein in normal adult tissue vary (Andersen et al, 2007;Lechler et al, 2007;Altieri, 2008). The results of the present study indicate that cytoplasmic expression of survivin is widespread in normal fetal and adult canine tissues and that it is nearly ubiquitous across canine lymphoma subtypes.…”

“…Some authors concede that survivin is expressed to some extent in adult tissues with a high cell turnover including testis, intestinal epithelium and bone marrow (Kobayashi et al, 1999). Evidence that the role of survivin is not restricted to developing tissues is emerging, with several reports of its expression in normal adult tissues (Fukuda and Pelus, 2006;Lechler et al, 2007).…”

Mechanisms of Renal Apoptosis in Health and Disease

“…36 Survivin, another IAP, has recently been identified as a constitutive prosurvival molecule in tubular cells that protects from experimental AKI. 37,38 …”