PDGF-D induces macrophage recruitment, increased interstitial pressure, and blood vessel maturation during angiogenesis

Abstract Platelet-derived growth factor-D (PDGF-D) is a recently characterized member of the PDGF family with unknown in vivo functions. We investigated the effects of PDGF-D in transgenic mice by expressing it in basal epidermal cells and then analyzed skin histology, interstitial fluid pressure, and wound healing. When compared with control mice, PDGF-D transgenic mice displayed increased numbers of macrophages and elevated interstitial fluid pressure in the dermis. Wound healing in the transgenic mice was characterized by increased cell density and enhanced recruitment of macrophages. Macrophage recruitment was also the characteristic response when PDGF-D was expressed in skeletal muscle or ear by an adeno-associated virus vector. Combined expression of PDGF-D with vascular endothelial growth factor-E (VEGF-E) led to increased pericyte/smooth muscle cell coating of the VEGF-E–induced vessels and inhibition of the vascular leakiness that accompanies VEGF-E–induced angiogenesis. These results show that full-length PDGF-D is activated in tissues and is capable of increasing interstitial fluid pressure and macrophage recruitment and the maturation of blood vessels in angiogenic processes.

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Inhibition of TGF-β modulates macrophages and vessel maturation in parallel to a lowering of interstitial fluid pressure in experimental carcinoma

Laboratory Investigation ◽

10.1038/labinvest.3700252 ◽

2005 ◽

Vol 85 (4) ◽

pp. 512-521 ◽

Cited By ~ 41

Author(s):

Alexei V Salnikov ◽

Pernilla Roswall ◽

Christian Sundberg ◽

Humphrey Gardner ◽

Nils-Erik Heldin ◽

...

Keyword(s):

Interstitial Fluid ◽

Fluid Pressure ◽

Interstitial Fluid Pressure ◽

Vessel Maturation ◽

Experimental Carcinoma

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Lymphangiogenesis Facilitates Initial Lymph Formation and Enhances the Dendritic Cell Mobilizing Chemokine CCL21 Without Affecting Migration

Arteriosclerosis Thrombosis and Vascular Biology ◽

10.1161/atvbaha.117.309883 ◽

2017 ◽

Vol 37 (11) ◽

pp. 2128-2135 ◽

Cited By ~ 8

Author(s):

Tine V. Karlsen ◽

Tore Reikvam ◽

Anne Tofteberg ◽

Elham Nikpey ◽

Trude Skogstrand ◽

...

Keyword(s):

Transgenic Mice ◽

Interstitial Fluid ◽

Fluid Pressure ◽

Lymphatic Vessels ◽

Interstitial Fluid Pressure ◽

Lymph Vessel ◽

Vessel Area ◽

Lymphatic Network ◽

Factor C ◽

Endothelial Growth Factor

Objective— Lymphatic vessels play an important role in body fluid, as well as immune system homeostasis. Although the role of malfunctioning or missing lymphatics has been studied extensively, less is known on the functional consequences of a chronically expanded lymphatic network or lymphangiogenesis. Approach and Results— To this end, we used K14-VEGF-C (keratin-14 vascular endothelial growth factor-C) transgenic mice overexpressing the vascular endothelial growth factor C in skin and investigated the responses to inflammatory and fluid volume challenges. We also recorded interstitial fluid pressure, a major determinant of lymph flow. Transgenic mice had a strongly enhanced lymph vessel area in skin. Acute inflammation induced by lipopolysaccharide and chronic inflammation by delayed-type hypersensitivity both resulted in increased interstitial fluid pressure and reduced lymph flow, both to the same extent in wild-type and transgenic mice. Hyperplastic lymphatic vessels, however, demonstrated enhanced transport capacity after local fluid overload not induced by inflammation. In this situation, interstitial fluid pressure was increased to a similar extent in the 2 strains, thus, suggesting that the enhanced lymph vessel area facilitated initial lymph formation. The increased lymph vessel area resulted in an enhanced production of the chemoattractant CCL21 that, however, did not result in augmented dendritic cell migration after induction of local skin inflammation by fluorescein isothiocyanate. Conclusions— An expanded lymphatic network is capable of enhanced chemoattractant production, and lymphangiogenesis will facilitate initial lymph formation favoring increased clearance of fluid in situations of augmented fluid filtration.

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Integrin αV β3 can substitute for collagen-binding β1 -integrins in vivo to maintain a homeostatic interstitial fluid pressure

Experimental Physiology ◽

10.1113/ep086902 ◽

2018 ◽

Vol 103 (5) ◽

pp. 629-634 ◽

Cited By ~ 2

Author(s):

Åsa Lidén ◽

Tine Veronika Karlsen ◽

Bengt Guss ◽

Rolf K. Reed ◽

Kristofer Rubin

Keyword(s):

Interstitial Fluid ◽

Fluid Pressure ◽

Interstitial Fluid Pressure ◽

Collagen Binding ◽

Integrin Αv ◽

Β1 Integrins

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The Mechanical Microenvironment in Breast Cancer

Cancers ◽

10.3390/cancers12061452 ◽

2020 ◽

Vol 12 (6) ◽

pp. 1452

Author(s):

Stephen J.P. Pratt ◽

Rachel M. Lee ◽

Stuart S. Martin

Keyword(s):

Breast Cancer ◽

Interstitial Fluid ◽

Fluid Pressure ◽

Normal Breast ◽

Interstitial Fluid Pressure ◽

Mechanical Stimuli ◽

Solid Stress ◽

Physical Cues

Mechanotransduction is the interpretation of physical cues by cells through mechanosensation mechanisms that elegantly translate mechanical stimuli into biochemical signaling pathways. While mechanical stress and their resulting cellular responses occur in normal physiologic contexts, there are a variety of cancer-associated physical cues present in the tumor microenvironment that are pathological in breast cancer. Mechanistic in vitro data and in vivo evidence currently support three mechanical stressors as mechanical modifiers in breast cancer that will be the focus of this review: stiffness, interstitial fluid pressure, and solid stress. Increases in stiffness, interstitial fluid pressure, and solid stress are thought to promote malignant phenotypes in normal breast epithelial cells, as well as exacerbate malignant phenotypes in breast cancer cells.

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