ProfessorRogerMason

Roger Mason is Emeritus Professor of Renal Medicine.  He was formerly Head of the Molecular Pathology Section and Professor of Biochemistry in the Division of Biomedical Sciences, Imperial College and, prior to that, Head of the Department of Biochemistry, Charing Cross and Westminster Medical School, University of London.

My overall aim has been to understand the role of the extracellular matrix in tissues and the mechanisms which underlie diseases in which an excessive matrix is laid down (e.g. fibrosis), or in which matrix is depleted (e.g. osteoarthritis). My current research seeks to understand the mechanisms of development of fibrosis in the kidney, especially in diabetic nephropathy.

We discovered that Connective Tissue Growth Factor (CTGF) expression is increased in glomerular mesangial cells exposed to diabetic conditions (high glucose) and in the glomeruli of kidneys of diabetic nephropathy patients and in non-obese diabetic (NOD) mice.  We showed that CTGF induces changes in human mesangial cells which recapitulate many of those which occur in diabetic nephropathy.  This raised questions about how CTGF exerts its actions.  We found that CTGF activates the neurotrophin receptor TrkA which, we discovered, is expressed in several types of kidney cell in diabetes.  This activation triggers intracellular signalling pathways, leading to induction of TIEG-1, a factor which increases signalling by the fibrosis-promoting factor TGF-beta in mesangial cells, and induces Snail-1 in kidney tubule epithelial cells, a factor which promotes fibrotic change in these cells. Thus CTGF, TrkA, and its downstream signalling pathway are attractive therapeutic targets. Our current investigations focus on whether knocking down expression of TrkA can prevent or ameliorate the development of diabetic nephropathy.

Whilst investigating the role of CTGF in the kidney we generated a transgenic mouse expressing CTGF under the control of the renin 1^c promoter. This developed a disorder closely resembling human cryoglobulinaemia, a disease associated with the production of abnormal antibodies (cryoglobulins) which block small blood vessels, causing glomerulonephritis in the kidney.  In ongoing research we are investigating how CTGF promotes this disease.