The role of hyperosmotic stress in inflammation and disease

Abstract

Hyperosmotic stress is an often overlooked process that potentially contributes to a number of human diseases. Whereas renal hyperosmolarity is a well-studied phenomenon, recent research provides evidence that many non-renal tissues routinely experience hyperosmotic stress that may contribute significantly to disease initiation and progression. Moreover, a growing body of evidence implicates hyperosmotic stress as a potent inflammatory stimulus by triggering proinflammatory cytokine release and inflammation. Under physiological conditions, the urine concentrating mechanism within the inner medullary region of the mammalian kidney exposes cells to high extracellular osmolarity. As such, renal cells have developed many adaptive strategies to compensate for increased osmolarity. Hyperosmotic stress is linked to many maladies, including acute and chronic, as well as local and systemic, inflammatory disorders. Hyperosmolarity triggers cell shrinkage, oxidative stress, protein carbonylation, mitochondrial depolarization, DNA damage, and cell cycle arrest, thus rendering cells susceptible to apoptosis. However, many adaptive mechanisms exist to counter the deleterious effects of hyperosmotic stress, including cytoskeletal rearrangement and up-regulation of antioxidant enzymes, transporters, and heat shock proteins. Osmolyte synthesis is also up-regulated and many of these compounds have been shown to reduce inflammation. The cytoprotective mechanisms and associated regulatory pathways that accompany the renal response to hyperosmolarity are found in many non-renal tissues, suggesting cells are commonly confronted with hyperosmotic conditions. Osmoadaptation allows cells to survive and function under potentially cytotoxic conditions. This review covers the pathological consequences of hyperosmotic stress in relation to disease and emphasizes the importance of considering hyperosmolarity in inflammation and disease progression.

Diabetic microangiopathy: Pathogenetic insights and novel therapeutic approaches

“…Here, the authors found that betaine (trimethylglycine), a natural specific type of zwitterion, known to improve visual acuity, has antioxidant properties and inhibits pathological neovascularization of human retinal microvascular endothelial cells exposed to high glucose levels, by attenuating ROS production, and subsequently suppressing both the VEGF receptor (VEGFR)-2 signaling pathway and VEGF production [3]. Betaine was, here, reported to act on the hyperosmolar component of hyperglycemia [4], a biophysical mechanism known to contribute to the development of microvascular disease in diabetes [5][6][7]. Thus, betaine would act on one pathway leading from hyperglycemia to microangiopathy.…”

Glycogen: A must have storage to survive stressful emergencies

“…1 Most organisms are exposed chronically or accidentally to high salinity environments and the ability to adapt to the availability of water is essential for life. In humans, many organs are exposed to water stress, due to water evaporation such as the skin, or through water osmosis into more concentrated aqueous environments due to physiological processes such as in kidneys, colon, and bladder.…”

Disease tolerance and immunity in host protection against infection

“…Osmotic stress, associated with systemic infections 43 , is sensed and regulated by the infected host, via several mechanisms including the activation of nuclear factor of activated T cells 5 (NFAT5) 44 (Figure 2). The osmotic stress response regulated by this transcription factor acts in a cytoprotective manner in parenchyma cells 45 , conferring tissue damage control in the kidney during systemic polymicrobial infections 46 and likely in the heart during infection with coxsackievirus 47 in mice ( Figure 2). …”