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Archives of Dermatological Research
Erschienen in: Archives of Dermatological Research 7/2013

01.09.2013 | Review Article

Molecular and cellular mechanisms of bone morphogenetic proteins and activins in the skin: potential benefits for wound healing

verfasst von: J. Moura, L. da Silva, M. T. Cruz, E. Carvalho

Erschienen in: Archives of Dermatological Research | Ausgabe 7/2013

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Abstract

Bone morphogenetic proteins (BMPs) and activins are phylogenetically conserved proteins, belonging to the transforming growth factor-β superfamily, that signal through the phosphorylation of receptor-regulated Smad proteins, activating different cell responses. They are involved in various steps of skin morphogenesis and wound repair, as can be evidenced by the fact that their expression is increased in skin injuries. BMPs play not only a role in bone regeneration but are also involved in cartilage, tendon-like tissue and epithelial regeneration, maintain vascular integrity, capillary sprouting, proliferation/migration of endothelial cells and angiogenesis, promote neuron and dendrite formation, alter neuropeptide levels and are involved in immune response modulation, at least in animal models. On the other hand, activins are involved in wound repair through the regulation of skin and immune cell migration and differentiation, re-epithelialization and granulation tissue formation, and also promote the expression of collagens by fibroblasts and modulate scar formation. This review aims at enunciating the effects of BMPs and activins in the skin, namely in skin development, as well as in crucial phases of skin wound healing, such as inflammation, angiogenesis and repair, and will focus on the effects of these proteins on skin cells and their signaling pathways, exploring the potential therapeutic approach of the application of BMP-2, BMP-6 and activin A in chronic wounds, particularly diabetic foot ulcerations.
Literatur
1.
Acosta JB, del Barco DG, Vera DC, Savigne W, Lopez-Saura P, Guillen Nieto G, Schultz GS (2008) The pro-inflammatory environment in recalcitrant diabetic foot wounds. Int Wound J 5(4):530–539PubMedCrossRef
2.
Ai X, Cappuzzello J, Hall AK (1999) Activin and bone morphogenetic proteins induce calcitonin gene-related peptide in embryonic sensory neurons in vitro. Mol Cell Neurosci 14(6):506–518PubMedCrossRef
3.
Al-Wahbi AM (2010) Impact of a diabetic foot care education program on lower limb amputation rate. Vasc Health Risk Manag 6:923–934PubMedCrossRef
4.
Anitha M, Shahnavaz N, Qayed E, Joseph I, Gossrau G, Mwangi S, Sitaraman SV, Greene JG, Srinivasan S (2010) BMP2 promotes differentiation of nitrergic and catecholaminergic enteric neurons through a Smad1-dependent pathway. Am J Physiol Gastrointest Liver Physiol 298(3):G375–G383PubMedCrossRef
5.
Antsiferova M, Klatte JE, Bodo E, Paus R, Jorcano JL, Matzuk MM, Werner S, Kogel H (2009) Keratinocyte-derived follistatin regulates epidermal homeostasis and wound repair. Lab Invest 89(2):131–141PubMedCrossRef
6.
Attisano L, Wrana JL (2002) Signal transduction by the TGF-beta superfamily. Science 296(5573):1646–1647PubMedCrossRef
7.
Au K, Ehrlich HP (2010) When the Smad signaling pathway is impaired, fibroblasts advance open wound contraction. Exp Mol Pathol 89(3):236–240PubMedCrossRef
8.
Bamberger C, Scharer A, Antsiferova M, Tychsen B, Pankow S, Muller M, Rulicke T, Paus R, Werner S (2005) Activin controls skin morphogenesis and wound repair predominantly via stromal cells and in a concentration-dependent manner via keratinocytes. Am J Pathol 167(3):733–747PubMedCrossRef
9.
Bandyopadhyay A, Yadav PS, Prashar P (2013) BMP signaling in development and diseases: A pharmacological perspective. Biochem Pharmacol 85(7):857–864PubMedCrossRef
10.
Beer HD, Gassmann MG, Munz B, Steiling H, Engelhardt F, Bleuel K, Werner S (2000) Expression and function of keratinocyte growth factor and activin in skin morphogenesis and cutaneous wound repair. J Investig Dermatol Symp Proc 5(1):34–39PubMedCrossRef
11.
Berlanga-Acosta J (2011) Diabetic lower extremity wounds: the rationale for growth factors-based infiltration treatment. Int Wound J 8(6):612–620PubMedCrossRef
12.
Bogdanski P, Pupek-Musialik D, Dytfeld J, Jagodzinski PP, Jablecka A, Kujawa A, Musialik K (2007) Influence of insulin therapy on expression of chemokine receptor CCR5 and selected inflammatory markers in patients with type 2 diabetes mellitus. Int J Clin Pharmacol Ther 45(10):563–567PubMed
13.
Botchkarev VA (2003) Bone morphogenetic proteins and their antagonists in skin and hair follicle biology. J Invest Dermatol 120(1):36–47PubMedCrossRef
14.
Botchkarev VA, Sharov AA (2004) BMP signaling in the control of skin development and hair follicle growth. Differ Res Biol Divers 72(9–10):512–526CrossRef
15.
Boulais N, Misery L (2008) The epidermis: a sensory tissue. Eur J Dermatol 18(2):119–127PubMed
16.
Bressan M, Davis P, Timmer J, Herzlinger D, Mikawa T (2009) Notochord-derived BMP antagonists inhibit endothelial cell generation and network formation. Dev Biol 326(1):101–111PubMedCrossRef
17.
Cassetta L, Cassol E, Poli G (2011) Macrophage polarization in health and disease. Sci World J 11:2391–2402CrossRef
18.
Chang H, Brown CW, Matzuk MM (2002) Genetic analysis of the mammalian transforming growth factor-beta superfamily. Endocr Rev 23(6):787–823PubMedCrossRef
19.
Cruise BA, Xu P, Hall AK (2004) Wounds increase activin in skin and a vasoactive neuropeptide in sensory ganglia. Dev Biol 271(1):1–10PubMedCrossRef
20.
Cunha SI, Pardali E, Thorikay M, Anderberg C, Hawinkels L, Goumans MJ, Seehra J, Heldin CH, ten Dijke P, Pietras K (2010) Genetic and pharmacological targeting of activin receptor-like kinase 1 impairs tumor growth and angiogenesis. J Exp Med 207(1):85–100PubMedCrossRef
21.
22.
Dani C (2013) Activins in adipogenesis and obesity. Int J Obes (Lond) 37(2):163–166CrossRef
23.
David L, Mallet C, Mazerbourg S, Feige JJ, Bailly S (2007) Identification of BMP9 and BMP10 as functional activators of the orphan activin receptor-like kinase 1 (ALK1) in endothelial cells. Blood 109(5):1953–1961PubMedCrossRef
24.
David L, Mallet C, Vailhe B, Lamouille S, Feige JJ, Bailly S (2007) Activin receptor-like kinase 1 inhibits human microvascular endothelial cell migration: potential roles for JNK and ERK. J Cell Physiol 213(2):484–489PubMedCrossRef
25.
Davis PJ (2009) The double-edged sword of the immune system–a force for good or evil in the wound? Int Wound J 6(4):241–245PubMedCrossRef
26.
de Kretser DM, O’Hehir RE, Hardy CL, Hedger MP (2012) The roles of activin A and its binding protein, follistatin, in inflammation and tissue repair. Mol Cell Endocrinol 359(1–2):101–106PubMedCrossRef
27.
28.
Dickinson S, Hancock DP, Petocz P, Ceriello A, Brand-Miller J (2008) High-glycemic index carbohydrate increases nuclear factor-kappaB activation in mononuclear cells of young, lean healthy subjects. Am J Clin Nutr 87(5):1188–1193PubMed
29.
Eming SA, Krieg T, Davidson JM (2007) Inflammation in wound repair: molecular and cellular mechanisms. J Invest Dermatol 127(3):514–525PubMedCrossRef
30.
Endo D, Kogure K, Hasegawa Y, Maku-uchi M, Kojima I (2004) Activin A augments vascular endothelial growth factor activity in promoting branching tubulogenesis in hepatic sinusoidal endothelial cells. J Hepatol 40(3):399–404PubMedCrossRef
31.
Fessing MY, Atoyan R, Shander B, Mardaryev AN, Botchkarev VV Jr, Poterlowicz K, Peng Y, Efimova T, Botchkarev VA (2010) BMP signaling induces cell-type-specific changes in gene expression programs of human keratinocytes and fibroblasts. J Invest Dermatol 130(2):398–404PubMedCrossRef
32.
Freinkel RK, Woodley D (2001) The biology of the skin. Parthenon Pub. Group, New York
33.
34.
Fumagalli M, Musso T, Vermi W, Scutera S, Daniele R, Alotto D, Cambieri I, Ostorero A, Gentili F, Caposio P, Zucca M, Sozzani S, Stella M, Castagnoli C (2007) Imbalance between activin A and follistatin drives postburn hypertrophic scar formation in human skin. Exp Dermatol 16(7):600–610PubMedCrossRef
35.
Funaba M, Ikeda T, Murakami M, Ogawa K, Abe M (2005) Up-regulation of mouse mast cell protease-6 gene by transforming growth factor-beta and activin in mast cell progenitors. Cell Signal 17(1):121–128PubMedCrossRef
36.
Funaba M, Ikeda T, Murakami M, Ogawa K, Tsuchida K, Sugino H, Abe M (2003) Transcriptional activation of mouse mast cell Protease-7 by activin and transforming growth factor-beta is inhibited by microphthalmia-associated transcription factor. J Biol Chem 278(52):52032–52041PubMedCrossRef
37.
Funaba M, Ikeda T, Ogawa K, Murakami M, Abe M (2003) Role of activin A in murine mast cells: modulation of cell growth, differentiation, and migration. J Leukoc Biol 73(6):793–801PubMedCrossRef
38.
Galiano RD, Tepper OM, Pelo CR, Bhatt KA, Callaghan M, Bastidas N, Bunting S, Steinmetz HG, Gurtner GC (2004) Topical vascular endothelial growth factor accelerates diabetic wound healing through increased angiogenesis and by mobilizing and recruiting bone marrow-derived cells. Am J Pathol 164(6):1935–1947PubMedCrossRef
39.
Game FL, Hinchliffe RJ, Apelqvist J, Armstrong DG, Bakker K, Hartemann A, Londahl M, Price PE, Jeffcoate WJ (2012) A systematic review of interventions to enhance the healing of chronic ulcers of the foot in diabetes. Diabetes/Metab Res Rev 28(Suppl 1):119–141CrossRef
40.
Ge J, Wang Y, Feng Y, Liu H, Cui X, Chen F, Tai G, Liu Z (2009) Direct effects of activin A on the activation of mouse macrophage RAW264.7 cells. Cell Mol Immunol 6(2):129–133PubMedCrossRef
41.
Gillitzer R, Goebeler M (2001) Chemokines in cutaneous wound healing. J Leukoc Biol 69(4):513–521PubMed
42.
Gold LI, Sung JJ, Siebert JW, Longaker MT (1997) Type I (RI) and type II (RII) receptors for transforming growth factor-beta isoforms are expressed subsequent to transforming growth factor-beta ligands during excisional wound repair. Am J Pathol 150(1):209–222PubMed
43.
Greenhalgh DG (1998) The role of apoptosis in wound healing. Int J Biochem Cell Biol 30(9):1019–1030PubMedCrossRef
44.
Gurtner GC, Werner S, Barrandon Y, Longaker MT (2008) Wound repair and regeneration. Nature 453(7193):314–321PubMedCrossRef
45.
Hall AK, Dinsio KJ, Cappuzzello J (2001) Skin cell induction of calcitonin gene-related peptide in embryonic sensory neurons in vitro involves activin. Dev Biol 229(2):263–270PubMedCrossRef
46.
Hayashi Y, Maeshima K, Goto F, Kojima I (2007) Activin A as a critical mediator of capillary formation: interaction with the fibroblast growth factor action. Endocr J 54(2):311–318PubMedCrossRef
47.
Heinke J, Wehofsits L, Zhou Q, Zoeller C, Baar KM, Helbing T, Laib A, Augustin H, Bode C, Patterson C, Moser M (2008) BMPER is an endothelial cell regulator and controls bone morphogenetic protein-4-dependent angiogenesis. Circ Res 103(8):804–812PubMedCrossRef
48.
Hirt-Burri N, Scaletta C, Gerber S, Pioletti DP, Applegate LA (2008) Wound-healing gene family expression differences between fetal and foreskin cells used for bioengineered skin substitutes. Artif Organs 32(7):509–518PubMedCrossRef
49.
Hogan BL (1996) Bone morphogenetic proteins in development. Curr Opin Genet Dev 6(4):432–438PubMedCrossRef
50.
Honda Y, Anada T, Kamakura S, Nakamura M, Sugawara S, Suzuki O (2006) Elevated extracellular calcium stimulates secretion of bone morphogenetic protein 2 by a macrophage cell line. Biochem Biophys Res Commun 345(3):1155–1160PubMedCrossRef
51.
Hong JH, Lee GT, Lee JH, Kwon SJ, Park SH, Kim SJ, Kim IY (2009) Effect of bone morphogenetic protein-6 on macrophages. Immunology 128(1 Suppl):e442–e450PubMedCrossRef
52.
Horbinski C, Stachowiak EK, Chandrasekaran V, Miuzukoshi E, Higgins D, Stachowiak MK (2002) Bone morphogenetic protein-7 stimulates initial dendritic growth in sympathetic neurons through an intracellular fibroblast growth factor signaling pathway. J Neurochem 80(1):54–63PubMedCrossRef
53.
Hubner G, Hu Q, Smola H, Werner S (1996) Strong induction of activin expression after injury suggests an important role of activin in wound repair. Dev Biol 173(2):490–498PubMedCrossRef
54.
Hwang EA, Lee HB, Tark KC (2001) Comparison of bone morphogenetic protein receptors expression in the fetal and adult skin. Yonsei Med J 42(6):581–586PubMed
55.
Ito Y, Sarkar P, Mi Q, Wu N, Bringas P Jr, Liu Y, Reddy S, Maxson R, Deng C, Chai Y (2001) Overexpression of Smad2 reveals its concerted action with Smad4 in regulating TGF-beta-mediated epidermal homeostasis. Dev Biol 236(1):181–194PubMedCrossRef
56.
57.
Kaiser S, Schirmacher P, Philipp A, Protschka M, Moll I, Nicol K, Blessing M (1998) Induction of bone morphogenetic protein-6 in skin wounds. Delayed reepitheliazation and scar formation in BMP-6 overexpressing transgenic mice. J Invest Dermatol 111(6):1145–1152PubMedCrossRef
58.
Kingsley DM (1994) The TGF-beta superfamily: new members, new receptors, and new genetic tests of function in different organisms. Genes Dev 8(2):133–146PubMedCrossRef
59.
Kirana S, Stratmann B, Prante C, Prohaska W, Koerperich H, Lammers D, Gastens MH, Quast T, Negrean M, Stirban OA, Nandrean SG, Gotting C, Minartz P, Kleesiek K, Tschoepe D (2012) Autologous stem cell therapy in the treatment of limb ischaemia induced chronic tissue ulcers of diabetic foot patients. Int J Clin Pract 66(4):384–393PubMedCrossRef
60.
Klopcic B, Maass T, Meyer E, Lehr HA, Metzger D, Chambon P, Mann A, Blessing M (2007) TGF-beta superfamily signaling is essential for tooth and hair morphogenesis and differentiation. Eur J Cell Biol 86(11–12):781–799PubMedCrossRef
61.
Knighton DR, Fiegel VD (1989) Macrophage-derived growth factors in wound healing: regulation of growth factor production by the oxygen microenvironment. Am Rev Respir Dis 140(4):1108–1111PubMedCrossRef
62.
Kozian DH, Ziche M, Augustin HG (1997) The activin-binding protein follistatin regulates autocrine endothelial cell activity and induces angiogenesis. Lab Invest 76(2):267–276PubMed
63.
Kwon SJ, Lee GT, Lee JH, Kim WJ, Kim IY (2009) Bone morphogenetic protein-6 induces the expression of inducible nitric oxide synthase in macrophages. Immunology 128(1 Suppl):e758–e765PubMedCrossRef
64.
Lamouille S, Mallet C, Feige JJ, Bailly S (2002) Activin receptor-like kinase 1 is implicated in the maturation phase of angiogenesis. Blood 100(13):4495–4501PubMedCrossRef
65.
Li G, Cui Y, McIlmurray L, Allen WE, Wang H (2005) rhBMP-2, rhVEGF(165), rhPTN and thrombin-related peptide, TP508 induce chemotaxis of human osteoblasts and microvascular endothelial cells. J Orthop Res 23(3):680–685PubMedCrossRef
66.
Lin SY, Morrison JR, Phillips DJ, de Kretser DM (2003) Regulation of ovarian function by the TGF-beta superfamily and follistatin. Reproduction 126(2):133–148PubMedCrossRef
67.
Liu D, Wang J, Kinzel B, Mueller M, Mao X, Valdez R, Liu Y, Li E (2007) Dosage-dependent requirement of BMP type II receptor for maintenance of vascular integrity. Blood 110(5):1502–1510PubMedCrossRef
68.
Liu ZJ, Velazquez OC (2008) Hyperoxia, endothelial progenitor cell mobilization, and diabetic wound healing. Antioxid Redox Signal 10(11):1869–1882PubMedCrossRef
69.
Maeshima K, Maeshima A, Hayashi Y, Kishi S, Kojima I (2004) Crucial role of activin a in tubulogenesis of endothelial cells induced by vascular endothelial growth factor. Endocrinology 145(8):3739–3745PubMedCrossRef
70.
Maric I, Poljak L, Zoricic S, Bobinac D, Bosukonda D, Sampath KT, Vukicevic S (2003) Bone morphogenetic protein-7 reduces the severity of colon tissue damage and accelerates the healing of inflammatory bowel disease in rats. J Cell Physiol 196(2):258–264PubMedCrossRef
71.
Martinez VG, Hernandez-Lopez C, Valencia J, Hidalgo L, Entrena A, Zapata AG, Vicente A, Sacedon R, Varas A (2010) The canonical BMP signaling pathway is involved in human monocyte-derived dendritic cell maturation. Immunol Cell Biol 89(5):610–618PubMedCrossRef
72.
Maruyama K, Asai J, Ii M, Thorne T, Losordo DW, D’Amore PA (2007) Decreased macrophage number and activation lead to reduced lymphatic vessel formation and contribute to impaired diabetic wound healing. Am J Pathol 170(4):1178–1191PubMedCrossRef
73.
74.
McCarthy SA, Bicknell R (1993) Inhibition of vascular endothelial cell growth by activin-A. J Biol Chem 268(31):23066–23071PubMed
75.
Mi Q, Riviere B, Clermont G, Steed DL, Vodovotz Y (2007) Agent-based model of inflammation and wound healing: insights into diabetic foot ulcer pathology and the role of transforming growth factor-beta1. Wound Repair Regen 15(5):671–682PubMedCrossRef
76.
Midwood KS, Williams LV, Schwarzbauer JE (2004) Tissue repair and the dynamics of the extracellular matrix. Int J Biochem Cell Biol 36(6):1031–1037PubMedCrossRef
77.
Moser M, Binder O, Wu Y, Aitsebaomo J, Ren R, Bode C, Bautch VL, Conlon FL, Patterson C (2003) BMPER, a novel endothelial cell precursor-derived protein, antagonizes bone morphogenetic protein signaling and endothelial cell differentiation. Mol Cell Biol 23(16):5664–5679PubMedCrossRef
78.
Munz B, Smola H, Engelhardt F, Bleuel K, Brauchle M, Lein I, Evans LW, Huylebroeck D, Balling R, Werner S (1999) Overexpression of activin A in the skin of transgenic mice reveals new activities of activin in epidermal morphogenesis, dermal fibrosis and wound repair. EMBO J 18(19):5205–5215PubMedCrossRef
79.
Munz B, Tretter YP, Hertel M, Engelhardt F, Alzheimer C, Werner S (2001) The roles of activins in repair processes of the skin and the brain. Mol Cell Endocrinol 180(1–2):169–177PubMedCrossRef
80.
Musso T, Scutera S, Vermi W, Daniele R, Fornaro M, Castagnoli C, Alotto D, Ravanini M, Cambieri I, Salogni L, Elia AR, Giovarelli M, Facchetti F, Girolomoni G, Sozzani S (2008) Activin A induces Langerhans cell differentiation in vitro and in human skin explants. PLoS ONE 3(9):e3271PubMedCrossRef
81.
Mustoe T (2004) Understanding chronic wounds: a unifying hypothesis on their pathogenesis and implications for therapy. Am J Surg 187(5A):65S–70SPubMedCrossRef
82.
Nagamine K, Furue M, Fukui A, Matsuda A, Hori T, Asashima M (2007) Blood cell and vessel formation following transplantation of activin-treated explants in Xenopus. Biol Pharm Bull 30(10):1856–1859PubMedCrossRef
83.
84.
Owens P, Han G, Li AG, Wang XJ (2008) The role of Smads in skin development. J Invest Dermatol 128(4):783–790PubMedCrossRef
85.
Pangas SA, Woodruff TK (2000) Activin signal transduction pathways. TEM 11(8):309–314PubMed
86.
Panopoulou E, Murphy C, Rasmussen H, Bagli E, Rofstad EK, Fotsis T (2005) Activin A suppresses neuroblastoma xenograft tumor growth via antimitotic and antiangiogenic mechanisms. Cancer Res 65(5):1877–1886PubMedCrossRef
87.
Pavelock KA, Girard BM, Schutz KC, Braas KM, May V (2007) Bone morphogenetic protein down-regulation of neuronal pituitary adenylate cyclase-activating polypeptide and reciprocal effects on vasoactive intestinal peptide expression. J Neurochem 100(3):603–616PubMedCrossRef
88.
Poulaki V, Mitsiades N, Kruse FE, Radetzky S, Iliaki E, Kirchhof B, Joussen AM (2004) Activin a in the regulation of corneal neovascularization and vascular endothelial growth factor expression. Am J Pathol 164(4):1293–1302PubMedCrossRef
89.
Raida M, Clement JH, Leek RD, Ameri K, Bicknell R, Niederwieser D, Harris AL (2005) Bone morphogenetic protein 2 (BMP-2) and induction of tumor angiogenesis. J Cancer Res Clin Oncol 131(11):741–750PubMedCrossRef
90.
Ren R, Charles PC, Zhang C, Wu Y, Wang H, Patterson C (2007) Gene expression profiles identify a role for cyclooxygenase 2-dependent prostanoid generation in BMP6-induced angiogenic responses. Blood 109(7):2847–2853PubMed
91.
Roberts AB, Russo A, Felici A, Flanders KC (2003) Smad3: a key player in pathogenetic mechanisms dependent on TGF-beta. Ann NY Acad Sci 995:1–10PubMedCrossRef
92.
Robson NC, Phillips DJ, McAlpine T, Shin A, Svobodova S, Toy T, Pillay V, Kirkpatrick N, Zanker D, Wilson K, Helling I, Wei H, Chen W, Cebon J, Maraskovsky E (2008) Activin-A: a novel dendritic cell-derived cytokine that potently attenuates CD40 ligand-specific cytokine and chemokine production. Blood 111(5):2733–2743PubMedCrossRef
93.
Rogers LC, Frykberg RG, Armstrong DG, Boulton AJ, Edmonds M, Van GH, Hartemann A, Game F, Jeffcoate W, Jirkovska A, Jude E, Morbach S, Morrison WB, Pinzur M, Pitocco D, Sanders L, Wukich DK, Uccioli L (2011) The Charcot foot in diabetes. J Am Podiatr Med Assoc 101(5):437–446PubMed
94.
Rothhammer T, Bataille F, Spruss T, Eissner G, Bosserhoff AK (2007) Functional implication of BMP4 expression on angiogenesis in malignant melanoma. Oncogene 26(28):4158–4170PubMedCrossRef
95.
Rotzer D, Krampert M, Sulyok S, Braun S, Stark HJ, Boukamp P, Werner S (2006) Id proteins: novel targets of activin action, which regulate epidermal homeostasis. Oncogene 25(14):2070–2081PubMedCrossRef
96.
Salogni L, Musso T, Bosisio D, Mirolo M, Jala VR, Haribabu B, Locati M, Sozzani S (2009) Activin A induces dendritic cell migration through the polarized release of CXC chemokine ligands 12 and 14. Blood 113(23):5848–5856PubMedCrossRef
97.
Scharpfenecker M, van Dinther M, Liu Z, van Bezooijen RL, Zhao Q, Pukac L, Lowik CW, ten Dijke P (2007) BMP-9 signals via ALK1 and inhibits bFGF-induced endothelial cell proliferation and VEGF-stimulated angiogenesis. J Cell Sci 120(Pt 6):964–972PubMedCrossRef
98.
Scutera S, Riboldi E, Daniele R, Elia AR, Fraone T, Castagnoli C, Giovarelli M, Musso T, Sozzani S (2008) Production and function of activin A in human dendritic cells. Eur Cytokine Netw 19(1):60–68PubMed
99.
Shao ES, Lin L, Yao Y, Bostrom KI (2009) Expression of vascular endothelial growth factor is coordinately regulated by the activin-like kinase receptors 1 and 5 in endothelial cells. Blood 114(10):2197–2206PubMedCrossRef
100.
Shi Y, Massague J (2003) Mechanisms of TGF-beta signaling from cell membrane to the nucleus. Cell 113(6):685–700PubMedCrossRef
101.
Sieveking DP, Ng MK (2009) Cell therapies for therapeutic angiogenesis: back to the bench. Vasc Med 14(2):153–166PubMedCrossRef
102.
103.
Soares R, Balogh G, Guo S, Gartner F, Russo J, Schmitt F (2004) Evidence for the notch signaling pathway on the role of estrogen in angiogenesis. Mol Endocrinol 18(9):2333–2343PubMedCrossRef
104.
Soares R, Guo S, Gartner F, Schmitt FC, Russo J (2003) 17 beta -estradiol-mediated vessel assembly and stabilization in tumor angiogenesis requires TGF beta and EGFR crosstalk. Angiogenesis 6(4):271–281PubMedCrossRef
105.
Stegenga ME, van der Crabben SN, Dessing MC, Pater JM, van den Pangaart PS, de Vos AF, Tanck MW, Roos D, Sauerwein HP, van der Poll T (2008) Effect of acute hyperglycaemia and/or hyperinsulinaemia on proinflammatory gene expression, cytokine production and neutrophil function in humans. Diabet Med 25(2):157–164PubMedCrossRef
106.
Stelnicki EJ, Longaker MT, Holmes D, Vanderwall K, Harrison MR, Largman C, Hoffman WY (1998) Bone morphogenetic protein-2 induces scar formation and skin maturation in the second trimester fetus. Plast Reconstr Surg 101(1):12–19PubMedCrossRef
107.
Stoitzner P, Stossel H, Wankell M, Hofer S, Heufler C, Werner S, Romani N (2005) Langerhans cells are strongly reduced in the skin of transgenic mice overexpressing follistatin in the epidermis. Eur J Cell Biol 84(8):733–741PubMedCrossRef
108.
Sulyok S, Wankell M, Alzheimer C, Werner S (2004) Activin: an important regulator of wound repair, fibrosis, and neuroprotection. Mol Cell Endocrinol 225(1–2):127–132PubMedCrossRef
109.
Suzuki Y, Ohga N, Morishita Y, Hida K, Miyazono K, Watabe T (2010) BMP-9 induces proliferation of multiple types of endothelial cells in vitro and in vivo. J Cell Sci 123(Pt 10):1684–1692PubMedCrossRef
110.
Symes AJ, Pitts RL, Conover J, Kos K, Coulombe J (2000) Synergy of activin and ciliary neurotrophic factor signaling pathways in the induction of vasoactive intestinal peptide gene expression. Mol Endocrinol 14(3):429–439PubMedCrossRef
111.
ten Dijke P, Hill CS (2004) New insights into TGF-beta-Smad signalling. Trends Biochem Sci 29(5):265–273PubMedCrossRef
112.
Thompson TB, Cook RW, Chapman SC, Jardetzky TS, Woodruff TK (2004) Beta A versus beta B: is it merely a matter of expression? Mol Cell Endocrinol 225(1–2):9–17PubMedCrossRef
113.
Thompson TB, Lerch TF, Cook RW, Woodruff TK, Jardetzky TS (2005) The structure of the follistatin:activin complex reveals antagonism of both type I and type II receptor binding. Dev Cell 9(4):535–543PubMedCrossRef
114.
Tsukazaki T, Chiang TA, Davison AF, Attisano L, Wrana JL (1998) SARA, a FYVE domain protein that recruits Smad2 to the TGFbeta receptor. Cell 95(6):779–791PubMedCrossRef
115.
Turns M (2011) The diabetic foot: an overview of assessment and complications. Br J Nurs 20(15):S19–S25PubMed
116.
117.
Urness LD, Sorensen LK, Li DY (2000) Arteriovenous malformations in mice lacking activin receptor-like kinase-1. Nat Genet 26(3):328–331PubMedCrossRef
118.
Wagner K, Peters M, Scholz A, Benckert C, Ruderisch HS, Wiedenmann B, Rosewicz S (2004) Activin A stimulates vascular endothelial growth factor gene transcription in human hepatocellular carcinoma cells. Gastroenterology 126(7):1828–1843PubMedCrossRef
119.
Wang D, Prakash J, Nguyen P, Davis-Dusenbery BN, Hill NS, Layne MD, Hata A, Lagna G (2012) Bone morphogenetic protein signaling in vascular disease: anti-inflammatory action through myocardin-related transcription factor A. J Biol Chem 287(33):28067–28077PubMedCrossRef
120.
Wang SY, Tai GX, Zhang PY, Mu DP, Zhang XJ, Liu ZH (2008) Inhibitory effect of activin A on activation of lipopolysaccharide-stimulated mouse macrophage RAW264.7 cells. Cytokine 42(1):85–91PubMedCrossRef
121.
Wankell M, Munz B, Hubner G, Hans W, Wolf E, Goppelt A, Werner S (2001) Impaired wound healing in transgenic mice overexpressing the activin antagonist follistatin in the epidermis. EMBO J 20(19):5361–5372PubMedCrossRef
122.
Werner S, Alzheimer C (2006) Roles of activin in tissue repair, fibrosis, and inflammatory disease. Cytokine Growth Factor Rev 17(3):157–171PubMedCrossRef
123.
Werner S, Beer HD, Mauch C, Luscher B (2001) The Mad1 transcription factor is a novel target of activin and TGF-beta action in keratinocytes: possible role of Mad1 in wound repair and psoriasis. Oncogene 20(51):7494–7504PubMedCrossRef
124.
Xu P, Hall AK (2006) The role of activin in neuropeptide induction and pain sensation. Dev Biol 299(2):303–309PubMedCrossRef
125.
Xu P, Hall AK (2007) Activin acts with nerve growth factor to regulate calcitonin gene-related peptide mRNA in sensory neurons. Neuroscience 150(3):665–674PubMedCrossRef
126.
Xu P, Van Slambrouck C, Berti-Mattera L, Hall AK (2005) Activin induces tactile allodynia and increases calcitonin gene-related peptide after peripheral inflammation. J Neurosci 25(40):9227–9235PubMedCrossRef
127.
Yan C, Grimm WA, Garner WL, Qin L, Travis T, Tan N, Han YP (2010) Epithelial to mesenchymal transition in human skin wound healing is induced by tumor necrosis factor-alpha through bone morphogenic protein-2. Am J Pathol 176(5):2247–2258PubMedCrossRef
128.
Yang L, Yamasaki K, Shirakata Y, Dai X, Tokumaru S, Yahata Y, Tohyama M, Hanakawa Y, Sayama K, Hashimoto K (2006) Bone morphogenetic protein-2 modulates Wnt and frizzled expression and enhances the canonical pathway of Wnt signaling in normal keratinocytes. J Dermatol Sci 42(2):111–119PubMedCrossRef
129.
Zhang C, Wang KZ, Qiang H, Tang YL, Li Q, Li M, Dang XQ (2010) Angiopoiesis and bone regeneration via co-expression of the hVEGF and hBMP genes from an adeno-associated viral vector in vitro and in vivo. Acta Pharmacol Sin 31(7):821–830PubMedCrossRef
130.
Zhang F, Qiu T, Wu X, Wan C, Shi W, Wang Y, Chen JG, Wan M, Clemens TL, Cao X (2009) Sustained BMP signaling in osteoblasts stimulates bone formation by promoting angiogenesis and osteoblast differentiation. J Bone Miner Res 24(7):1224–1233PubMedCrossRef
131.
Zhang M, Liu NY, Wang XE, Chen YH, Li QL, Lu KR, Sun L, Jia Q, Zhang L, Zhang L (2011) Activin B promotes epithelial wound healing in vivo through RhoA-JNK signaling pathway. PLoS ONE 6(9):e25143PubMedCrossRef
132.
Zhou Q, Heinke J, Vargas A, Winnik S, Krauss T, Bode C, Patterson C, Moser M (2007) ERK signaling is a central regulator for BMP-4 dependent capillary sprouting. Cardiovasc Res 76(3):390–399PubMedCrossRef
Metadaten
Titel
Molecular and cellular mechanisms of bone morphogenetic proteins and activins in the skin: potential benefits for wound healing
verfasst von
J. Moura
L. da Silva
M. T. Cruz
E. Carvalho
Publikationsdatum
01.09.2013
Verlag
Springer Berlin Heidelberg
Erschienen in
Archives of Dermatological Research / Ausgabe 7/2013
Print ISSN: 0340-3696
Elektronische ISSN: 1432-069X
DOI
https://doi.org/10.1007/s00403-013-1381-2

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