ABSTRACT
Introduction 374
Historical Perspective 375
The “Ground Substance” Era 375
“Mucopolysaccharide” Period 376
Discovery of HA (Hyaluronan) 376
The Modern Era 376
The Postmodern Period 377
Biology of Hyaluronan 377
Overview 377
Structure and Terminology 378
Function 379
General 379
Embryonic Development 380
Wound Healing 381
Carcinogenesis 381
Aging 381
Hyaladherins 382
Hyaluronan in the ECM 383
Intracellular Hyaluronan 383
Hyaluronan Receptors 384
CD44 384
RHAMM 385
Hyaluronan in Skin 385
Artifacts of Hyaluronan Histolocalization in Skin 385
Epidermal Hyaluronan 386
Dermal Hyaluronan 387
Aging Skin 387
Photoaging of Skin 388
Acute and Chronic Inflammation 388
Hyaluronan in Skin Substitutes 389
Hyaluronan Synthases 390
Hyaluronan Catabolism 390
The Hyaluronidases 390
Non-enzymatic Degradation 391
Hyaluronidase Inhibitors 391
Macromolecular Inhibitors 391
Low Molecular Weight Inhibitors 392
Oxidative Stress and Skin Hyaluronan 393
Enhancing Skin Moisture by Modulating Hyaluronan 394
Alpha-Hydroxy Acids 394
Retinoic Acid and Its Derivatives 394
Steroids 395
General Comments from Dermatology and Cosmetic Perspectives 395
Future Developments 396
References 396
INTRODUCTION
Skin is a large and complex tissue, with a vast range of functions that interfaces
with a hostile environment. The mechanisms that underlie the resilience of skin to
the harsh outside world, and the extraordinary ability of the skin to also protect
underlying tissues are just beginning to be understood. Skin retains a large
amount of water, and much of the external trauma to which it is constantly
subjected, in addition to the normal process of aging, causes loss of moisture.
The key molecule involved in skin moisture is hyaluronan (hyaluronic acid,
HA) with its associated water-of-hydration. Understanding the metabolism
of HA, its reactions within skin, and the interactions of HA with other
skin components will facilitate the ability to modulate skin moisture in a
rational manner, different from the empirical attempts that have been utilized
up to now.
