We are studying the role of connective tissue growth factor (CTGF) in fibrotic diseases, which are characterized by excessive production and deposition of insoluble collagen matrix, resulting in loss of tissue structure and organ dysfunction. Our main research efforts are currently focussed on liver and pancreatic fibrosis but we have collaborative efforts that focus on other organ systems such as the lung, intestine, heart and skin. Using molecular, cellular and biochemical approches, both in vitro and in vivo, our goals are to understand the mechanisms by which CTGF stimulates collagen production by fibrogenic cells types. In this manner, we will determine the therapeutic value of targetting pathways of CTGF biosynthesis or action to treat a variety of fibrotic disorders.
Charrier AL; Brigstock DR. 2010. Connective tissue growth factor production by activated pancreatic stellate cells in mouse alcoholic chronic pancreatitis. Laboratory Investigation; A Journal Of Technical Methods And Pathology. Vol. 90, no. 8. (August): e1179.
Brigstock DR. 2010. Connective tissue growth factor (CCN2, CTGF) and organ fibrosis: lessons from transgenic animals. Journal Of Cell Communication And Signaling. Vol. 4, no. 1. (March): e1.
Tong Z; Chen R; Alt DS; Kemper S; Perbal B; Brigstock DR. 2009. Susceptibility to liver fibrosis in mice expressing a connective tissue growth factor transgene in hepatocytes. Hepatology (Baltimore, Md.). Vol. 50, no. 3. (September): e939.
Wang J; Leclercq I; Brymora JM; Xu N; Ramezani-Moghadam M; London RM; Brigstock D; George J. 2009. Kupffer cells mediate leptin-induced liver fibrosis. Gastroenterology. Vol. 137, no. 2. (August): e713.
Gao RP; Brigstock DR. 2009. Connective tissue growth factor hammerhead ribozyme attenuates human hepatic stellate cell function. World Journal Of Gastroenterology: WJG. Vol. 15, no. 30. (August): e3807.
Zhou Y; Brigstock D; Besner GE. 2009. Heparin-binding EGF-like growth factor is a potent dilator of terminal mesenteric arterioles. Microvascular Research. Vol. 78, no. 1. (June): e78.
Brigstock DR. 2009. Strategies for blocking the fibrogenic actions of connective tissue growth factor (CCN2): From pharmacological inhibition in vitro to targeted siRNA therapy in vivo. Journal Of Cell Communication And Signaling. Vol. 3, no. 1. (March): e5.
Liu J; Xu W; Sun T; Wang F; Puscheck E; Brigstock D; Wang QT; Davis R; Rappolee DA. 2009. Hyperosmolar stress induces global mRNA responses in placental trophoblast stem cells that emulate early post-implantation differentiation. Placenta. Vol. 30, no. 1. (January): e66.
Leask A, Chen S, Pala D, Brigstock DR. 2008. Regulation of CCN2 mRNA expression and promoter activity in activated hepatic stellate cells. J Cell Commun Signal.. Vol. 2, no. 1-2. (June): 49-56.
Boag JM; Beesley AH; Firth MJ; Freitas JR; Ford J; Brigstock DR; de Klerk NH; Kees UR. 2007. High expression of connective tissue growth factor in pre-B acute lymphoblastic leukaemia. British Journal Of Haematology. Vol. 138, no. 6. (September): e740.
Cooker LA; Peterson D; Rambow J; Riser ML; Riser RE; Najmabadi F; Brigstock D; Riser BL. 2007. TNF-alpha, but not IFN-gamma, regulates CCN2 (CTGF), collagen type I, and proliferation in mesangial cells: possible roles in the progression of renal fibrosis. American Journal Of Physiology. Renal Physiology. Vol. 293, no. 1. (July): eF157.
Baran CP; Opalek JM; McMaken S; Newland CA; O'Brien JM Jr; Hunter MG; Bringardner BD; Monick MM; Brigstock DR; Stromberg PC; Hunninghake GW; Marsh CB. 2007. Important roles for macrophage colony-stimulating factor, CC chemokine ligand 2, and mononuclear phagocytes in the pathogenesis of pulmonary fibrosis. American Journal Of Respiratory And Critical Care Medicine. Vol. 176, no. 1. (July): e78.
Gao R; Brigstock DR. 2006. A novel integrin alpha5beta1 binding domain in module 4 of connective tissue growth factor (CCN2/CTGF) promotes adhesion and migration of activated pancreatic stellate cells. Gut. Vol. 55, no. 6. (June): e856.
Csencsits K; Wood SC; Lu G; Faust SM; Brigstock D; Eichwald EJ; Orosz CG; Bishop DK. 2006. Transforming growth factor beta-induced connective tissue growth factor and chronic allograft rejection. American Journal Of Transplantation: Official Journal Of The American Society Of Transplantation And The American Society Of Transplant Surgeons. Vol. 6, no. 5 Pt 1. (May): e959.
Tong ZY; Brigstock DR. 2006. Intrinsic biological activity of the thrombospondin structural homology repeat in connective tissue growth factor. The Journal Of Endocrinology. Vol. 188, no. 3. (March): eR1.
Gao R; Brigstock DR. 2005. Activation of nuclear factor kappa B (NF-kappaB) by connective tissue growth factor (CCN2) is involved in sustaining the survival of primary rat hepatic stellate cells. Cell Communication And Signaling: CCS. Vol. 3, no. November: e14.
Gao R; Brigstock DR. 2005. Connective tissue growth factor (CCN2) in rat pancreatic stellate cell function: integrin alpha5beta1 as a novel CCN2 receptor. Gastroenterology. Vol. 129, no. 3. (September): e1019.
Cicha I; Yilmaz A; Klein M; Raithel D; Brigstock DR; Daniel WG; Goppelt-Struebe M; Garlichs CD. 2005. Connective tissue growth factor is overexpressed in complicated atherosclerotic plaques and induces mononuclear cell chemotaxis in vitro. Arteriosclerosis, Thrombosis, And Vascular Biology. Vol. 25, no. 5. (May): e1008.
Brigstock D; Lau L; Perbal B. 2005. Report and abstracts of the 3rd International Workshop on the CCN Family of Genes. St Malo, France, 20-23 October 2004. Journal Of Clinical Pathology. Vol. 58, no. 5. (May): e463.
KÃ¶ninger J; di Mola FF; Di Sebastiano P; Gardini A; Brigstock DR; Innocenti P; BÃ¼chler MW; Friess H. 2005. Transforming growth factor-beta pathway is activated in cholecystolithiasis. Langenbeck's Archives Of Surgery / Deutsche Gesellschaft FÃ¼r Chirurgie. Vol. 390, no. 1. (February): e21.
Rachfal AW; Brigstock DR. 2005. Structural and functional properties of CCN proteins. Vitamins And Hormones. Vol. 70, no. January: e69.
Rachfal AW; Luquette MH; Brigstock DR. 2004. Expression of connective tissue growth factor (CCN2) in desmoplastic small round cell tumour. Journal Of Clinical Pathology. Vol. 57, no. 4. (April): e422.
Gao R; Brigstock DR. 2004. Connective tissue growth factor (CCN2) induces adhesion of rat activated hepatic stellate cells by binding of its C-terminal domain to integrin alpha(v)beta(3) and heparan sulfate proteoglycan. The Journal Of Biological Chemistry. Vol. 279, no. 10. (March): e8848.