title: Angiogenesis in the skin of SHARPIN-deficient mice with chronic proliferative dermatitis.
abstract: Angiogenesis is a common feature of pathological processes including wound healing, tumor formation, and chronic inflammation. Chronic inflammation can also be associated with dilation or proliferation of lymph vessels. We examined blood vessels and lymphatics and the expression of pro- and anti-angiogenic genes in the skin of SHARPIN-deficient mice which spontaneously develop a chronic proliferative dermatitis (cpdm). The number of blood vessels in the dermis of cpdm mice increased with age as the inflammation progressed. Lymphatics identified by labeling for LYVE1 and podoplanin were moderately dilated, but they were not increased in number. The expression of proangiogenic Vegfa, Flt1 and anti-angiogenic Sema3a mRNA was increased. VEGFA was primarily localized in keratinocytes of cpdm skin. There was also increased expression of Ece1 and Pdpn mRNA. Podoplanin was restricted to lymphatic endothelial cells in normal skin, but fibroblasts in cpdm skin also reacted with anti-podoplanin antibodies indicating that they were activated. The expression of other angiogenic and lymphangiogenic factors was not altered or decreased. These results indicate that cpdm mice may be a useful model to study the pathogenesis of angiogenesis in chronic inflammation.
authors: Department of Comparative Pathobiology, College of Veterinary Medicine, Purdue University, West Lafayette, IN 47907, United States; Purdue Institute for Immunology, Inflammation and Infectious Diseases, Purdue University, West Lafayette, IN 47907, United States; The Jackson Laboratory, Bar Harbor, ME 04609, United States. Electronic address: hogenesch@purdue.edu.
authors: Harm
authors: H
authors: HogenEsch
authors: Department of Comparative Pathobiology, College of Veterinary Medicine, Purdue University, West Lafayette, IN 47907, United States.
authors: Mario
authors: M
authors: Sola
authors: The Jackson Laboratory, Bar Harbor, ME 04609, United States.
authors: Timothy M
authors: TM
authors: Stearns
authors: The Jackson Laboratory, Bar Harbor, ME 04609, United States.
authors: Kathleen A
authors: KA
authors: Silva
authors: The Jackson Laboratory, Bar Harbor, ME 04609, United States.
authors: Victoria E
authors: VE
authors: Kennedy
authors: Department of Comparative Pathobiology, College of Veterinary Medicine, Purdue University, West Lafayette, IN 47907, United States; The Jackson Laboratory, Bar Harbor, ME 04609, United States.
authors: John P
authors: JP
authors: Sundberg
mesh_terms: D000818:Animals; D002352:Carrier Proteins / Q000235:genetics*; D003872:Dermatitis / Q000378:metabolism* / Q000473:pathology; D042783:Endothelial Cells / Q000378:metabolism; D000072396:Endothelin-Converting Enzymes / Q000235:genetics / Q000378:metabolism; D005260:Female; D005347:Fibroblasts / Q000378:metabolism; D006023:Glycoproteins / Q000235:genetics / Q000378:metabolism; D047908:Intracellular Signaling Peptides and Proteins; D015603:Keratinocytes / Q000378:metabolism; D042601:Lymphatic Vessels / Q000473:pathology; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism; D026901:Membrane Transport Proteins; D051379:Mice; D008810:Mice, Inbred C57BL; D009389:Neovascularization, Pathologic / Q000378:metabolism*; D040121:Semaphorin-3A / Q000235:genetics / Q000378:metabolism; D012867:Skin / Q000098:blood supply* / Q000166:cytology / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000235:genetics / Q000378:metabolism; D000098853:Podoplanin
chemical_list: D002352:Carrier Proteins; D000072396:Endothelin-Converting Enzymes; D006023:Glycoproteins; D047908:Intracellular Signaling Peptides and Proteins; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D040121:Semaphorin-3A; D042461:Vascular Endothelial Growth Factor A; D040281:Vascular Endothelial Growth Factor Receptor-1; C490441:Pdpn protein, mouse; D000098853:Podoplanin; C488217:Sema3a protein, mouse; C554944:Sipl1 protein, mouse; C492273:LYVE1 protein, mouse; C501163:Flt1 protein, mouse; C000606925:Ece1 protein, mouse
keywords: Angiogenesis; Dermatitis; Lymphangiogenesis; Podoplanin; VEGF