The glycoseaminoglycan (GAG) hyaluronan (HA) is an important structural component of the extracellular matrix, but also interacts with cells during important events in normal and pathological conditions such as embryonic development, wound healing, inflammation and cancer. HA has a unique hydration capacity and in the last decade it was revealed that in the HA rich interstitium of the renal medulla the HA level is rapidly changed depending on the body hydration status while that of the cortex remains unchanged at very low amounts. The kidney uses HA dynamically for the regulation of whole-body fluid homeostasis. During hyadration renomedullary HA increases and during dehydration the opposite occurs. The changes in the physico-chemical characteristics of the interstitial space affects fluid flux i.e. reabsorption. Some classical hormones involed in renal fluid handling are important regulators of HA turn-over during variations in hydration status. One major producer of HA in the kidney is the renomedullary interstitial cell. During several kidney disease states, such as for example transplant rejection and diabetes, HA is upregulated, contributing to an abnormal phenotype. The use of hyaluronidase to reduce pathologically over-expressed levels of tissue HA is a potential therapeutic tool since diuretics are less efficient to remove water bound to HA in the interstitium. The majority of data describing the role of HA originates from animal and cell studies, but the available data from humans demonstrate an upregulation of HA in diabetic kidneys, in transplant-rejected kidneys and during acute tubular necrosis. This review summarizes the current knowledge regarding interstitial HA in regulating kidney structure and function during normal and pathological conditions. It encompasses mechanistic insights into the heterogeneous intrarenal distribution of HA i.e. late nephrogenesis, its regulation during variations in hydration status, and during several pathological conditions. Changes in hyaluronan synthases, hyaluronidases and CD44 expression are discussed in parallel.
- hydration status
- Copyright © 2011, American Journal of Physiology - Regulatory, Integrative and Comparative Physiology