Regulation of Lymphatic Capillary Regeneration

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Regulation of Lymphatic Capillary Regeneration

Postby patoco » Thu Jan 04, 2007 12:10 am

Regulation of Lymphatic Capillary Regeneration by Interstitial Flow in Skin.

Am J Physiol Heart Circ Physiol. 2006 Dec 22

Goldman J, Conley KA, Raehl A, Bondy DM, Pytowski B, Swartz MA,
Rutkowksi JM, Jaroch DB, Ongstad EL. Biomedical Engineering, Michigan Technological University, Houghton, Michigan, United States.

Decreased interstitial flow (IF) in secondary lymphedema is coincident
with poor physiological lymphatic regeneration. However, both the
existence and direction of causality between IF and lymphangiogenesis
remain unclear. This is primarily because the role of IF and its
importance relative to the action of the pro-lymphangiogenic growth
factor VEGF-C (which signals primarily through its receptor VEGFR-3)
are poorly understood. To clarify this, we explored the cooperative
roles of VEGFR-3 and IF in a mouse model of lymphangiogenesis in
regenerating skin. Specifically, a region of lymphangiogenesis was
created by substituting a portion of mouse tail skin with a collagen
gel within which lymphatic capillaries completely regenerate over a
period of 60 days.

The relative importance of IF and VEGF-C signaling were evaluated by
either inhibiting VEGFR-3 signaling with antagonistic antibodies or by
reducing IF. In some cases, VEGF-C signaling was then increased with
exogenous protein. In order to clarify the role of IF, the distribution
of endogenous matrix metalloproteinases (MMPs) and VEGF-C within the
regenerating region were determined.

It was found that inhibition of either VEGFR-3 or IF suppressed
endogenous lymphangiogenesis. Reduction of IF was found to decrease
lymphatic migration and transport of endogenous MMP and VEGF-C through the regenerating region. Therapeutic VEGF-C administration restored lymphangiogenesis following inhibition of VEGFR-3 but did not increase lymphangiogenesis following inhibition of IF. These results identify IF as an important regulator of the pro-lymphangiogenic action of VEGF-C.

Key words: VEGFR-3, endothelial , lymphangiogenesis, Interstitial Flow.

PMID: 17189348 [PubMed - as supplied by publisher] ... etrieve&...


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