HYPOXIA AND ERYTHROPOIETIN IN THE REGULATION OF AQUAPORINS

MALTANERI ROMINA; VITTORI DANIELA; NESSE ALCIRA; VOTA DAIANA, CHAMORRO MARÍA EUGENIA, CALLERO MARIANA, NESSE ALCIRA, VITTORI DANIELA

Advances in Medicine and Biology

NOVA Medicine and Health

Lugar: Nueva York; Año: 2020; p. 53 - 98

Chapter 2: AbstractAquaporins (AQPs) constitute a familyof small transmembrane proteins that facilitate osmotically-driven watertransport, and in some cases that of small solutes. Several roles for AQPs havebeen identified, such as the regulation of brain and corneal water balance,neural signal transduction and angiogenesis. Moreover, various members of thisfamily have been found in high-grade tumors of different tissue origins.Although recent investigations have shed light on the structure and function ofAQPs, many aspects of their regulation remain to be explored. Accumulating evidence places hypoxiaas a modulator of AQP expression in different tissues, and some members of thisfamily have been shown to contain hypoxia-responsive sequence elements in theirpromoters. However, there is still little knowledge about the signalingpathways relaying information on O2 homeostasis to the aquaporingene. The maintenance of adequate O2levels is essential to support cellular function. Hypoxia results from animbalance between the supply of O2 to the tissues and itsconsumption, which may be the outcome of pathological conditions such asobstructive apnea, anemia, ischemia and atherosclerosis. Through theupregulation of the hypoxia-inducible transcription factor, cells undergoingchronic hypoxic stress can modulate the expression levels of genes related tometabolism, cell proliferation, differentiation and apoptotic cell death.Hypoxia can also drive tumor growth and vascularization, thus compromising theefficacy of treatments. Erythropoietin is the paradigm ofhypoxia-inducible gene expression, as it drives the increase of erythrocytemass in response to low O2 levels. However, the finding oferythropoietin receptors in various cell types shows its biological relevancegoes beyond the erythroid compartment. Erythropoietin is regarded as aproangiogenic factor, as well as a tissue protectant from hypoxic/ischemicinjuries. Although there is scarce experimental evidence supporting themodulation of AQPs by erythropoietin, some of these water channels have beenshown to participate in the biological effects of the growth factor, such asAQP1 inendothelial cell migration and AQP4 in the prevention of edema and ischemic damage in therat brain.This Chapter will emphasize theevidence of AQP modulation by hypoxia and erythropoietin, as these waterchannels are increasingly valued as potential biomarkers of disease, as well aspharmacological targets for the treatment of brain and renal injuries,cardiovascular disorders and cancer.