Characterization of Lymphangiogenesis in a Model of Adult Skin Regeneration

Characterization of Lymphangiogenesis in a Model of Adult Skin Regeneration

Rutkowski JM, Boardman KC, Swartz MA; 2006

Synopsis: This paper describes the process of the formation of lymphatic vessels in adults, including its dependence on interstitial fluid flow for vessel organization and the effects of environmental factors on lymphatic capillary evolution.

Abstract: To date, adult lymphangiogenesis is not well understood. In this study we describe the evolution of lymphatic capillaries in regenerating skin and correlate lymphatic migration and organization with the expression of matrix metallopro- teinases (MMPs), immune cells, the growth factors VEGF-A and VEGF-C, and the heparan sulfate proteogylcan perlecan, a key com- ponent of basement membrane. We show that while lymphatic endo- thelial cells (LECs) migrate and organize unidirectionally, in the direction of interstitial fluid flow, they do not sprout into the region but rather migrate as single cells that later join together into vessels. Furthermore, in a modified shunted flow version of the model, infiltrated LECs fail to organize into functional vessels, indicating that interstitial fluid flow is necessary for lymphatic organization. Perlecan expression on new lymphatic vessels was only observed after vessel organization was complete and also appeared first in the distal region, consistent with the directionality of lymphatic migration and organi- zation. VEGF-C expression peaked at the initiation of lymphangio- genesis but was reduced to lower levels throughout organization and maturation. In mice lacking MMP-9, lymphatics regenerated nor- mally, suggesting that MMP-9 is not required for lymphangiogenesis, at least in mouse skin. This study thus characterizes the process of adult lymphangiogenesis and differentiates it from sprouting blood angiogenesis, verifies its dependence on interstitial fluid flow for vessel organization, and correlates its temporal evolution with those of relevant environmental factors.

APA Citation: Rutkowski, J. (2006). Characterization of lymphangiogenesis in a model of adult skin regeneration. AJP: Heart And Circulatory Physiology, 291(3), H1402-H1410. http://dx.doi.org/10.1152/ajpheart.00038.2006

AMA Citation: Rutkowski J. Characterization of lymphangiogenesis in a model of adult skin regeneration. AJP: Heart and Circulatory Physiology. 2006;291(3):H1402-H1410. doi:10.1152/ajpheart.00038.2006.