Rejuvenating Hydrator: Restoring Epidermal Hyaluronic Acid Homeostasis With Instant Benefits

January 2016 | Volume 15 | Issue 1 | Supplement Individual Articles | 24 | Copyright © January 2016


Vic A. Narurkar MD,a Sabrina G. Fabi MD FAAD FAACS,b Vivian W. Bucay MD FAAD,c Ruth Tedaldi MD,d Jeanine B. Downie MD,e Joshua A. Zeichner MD,f Kimberly Butterwick MD,g Amy Taub MD,h Kuniko Kadoya PhD,i Elizabeth T. Makino BS MBA CCRA,i Rahul C. Mehta PhD,i and Virginia L. Vega PhDi

aBay Area Laser Institute, San Francisco, CA
bDepartment of Dermatology, University of California San Diego, CA
cBucay Center for Dermatology and Aesthetics, San Antonio, TX
dDermatology Partners, Inc, Wellesley, MA
eImage Dermatology, Montclair, NJ
fDepartment of Dermatology, Mount Sinai Hospital, New York, NJ
gCosmetic Laser Dermatology, La Jolla, CA
hAdvanced Dermatology, Lincolshire, IL
iResearch & Development, SkinMedica Inc., an Allergan Company, Irvine, CA

table 2
is not clear but it may enhance HYAL1 degradation activity. Activities of HYAL1 and HYAL2 depend on HA-CD44 association, which strongly suggests that HA-degradation is a receptor mediated process.19 The role of extracellular HYALs in HA degradation is still controversial as HA-degradation products are rarely detected outside the cells in vivo.20-22 The final destination of HA catabolic processes is different in the epidermis and dermis. In the epidermis, HA is mainly degraded intracellularly after endocytic internalization, while in the dermis HA-fragments are predominantly drained by afferent lymphatic vessels or uptaken via a receptor-mediated process by the endothelium.23 Non-enzymatic depolymerization of extracellular HA is accomplished by reactive oxygen species (ROS) in the presence of reducing agents such as ascorbic acid, thiols, ferrous, or cuprous ions, and by Maillard products (that are also involved in the formation of advanced glycation endproducts).24

CD44: THE MAIN HYALURONIC ACID RECEPTOR

Hyaluronic acid binds to an ubiquitous, abundant, and functionally important family of cell surface receptors called CD44. CD44 is encoded by a single gene in which alternative splicing determines variations within different cell types. Binding of HA to CD44 requires the activation of the latter by removal of the sialic acid,25 which suggests a very tight regulation in the activation of HA-CD44 signaling. HA-CD44 interactions activate unique signal transduction pathways that initiate a concomitant onset of multiple cellular functions. Two major intracellular signaling pathways (RhoA-ROK vs Rac-PKN) are partially responsible for the selective control of a variety of HA-linked functions such as proliferation, survival, migration, cell-cell adhesion, and barrier formation. Recent evidence suggests that the size of HA that binds to CD44 is a key factor in triggering a specific intracellular signal transduction pathway under physiological or pathological conditions such as skin atrophy, psoriasis, atopic dermatitis, actinic keratosis, and chronic non-healing wounds.26
In addition, a close relationship exists between CD44 expression and HA levels in the skin. For example, it has been reported that a significant reduction of HA levels is observed