Mesangial cell proliferation inhibitors for the treatment of proliferative glomerular disease.
Mesangial cells (MC) serve a number of functions in the renal glomerular capillary including structural support of the capillary tuft, modulation of glomerular hemodynamics, and a phagocytic function allowing removal of macromolecules and immune complexes. The proliferation of MC is a prominent feature of glomerular disease including IgA nephropathy, membranoproliferative glomerulonephritis, lupus nephritis, and diabetic nephropathy. In experimental animal models of nephritis, MC proliferation frequently precedes and is linked to the increase of extracellular matrix in the mesangium and glomerulosclerosis. Reduction of MC proliferation in glomerular disease models by treatment with heparin, low-protein diet, or antibodies to platelet-derived growth factor (PDGF), have been shown to reduce extracellular matrix expansion and glomerulosclerotic changes. Therefore, MC proliferation inhibitors may offer therapeutic opportunities for the treatment of proliferative glomerular disease. It is also known that the MC proliferation is inhibited by many kinds of pharmacological drugs, for example, angiotensin converting enzyme (ACE) inhibitors, leukotriene D(4) (LTD(4)) antagonists, PDGF inhibitors, matrix metalloproteinases (MMP) inhibitors, 3-hydroxy-3 methyl glutaryl-coenzymeA (HMG-CoA) inhibitors, cyclin-dependent kinases (CDK) inhibitors, and others. This review summarizes the recently reported MC proliferation inhibitors with their pharmacological properties on the basis of their chemical structures.
Kurogi
Yasuhisa
Y
Otsuka Pharmaceutical Co, Ltd, R&D Alliances, 463-10, Kagasuno, Kawauchi-cho, Tokushima 771-0192, Japan. y_kurogi@research.otuska.co.jp
D000804:Angiotensin II / Q000378:metabolism; D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D002121:Calcium Channel Blockers / Q000494:pharmacology / Q000627:therapeutic use; D002455:Cell Division / Q000187:drug effects*; D004791:Enzyme Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D005920:Glomerular Mesangium / Q000473:pathology*; D005922:Glomerulonephritis, IGA / Q000188:drug therapy*; D015432:Glomerulonephritis, Membranoproliferative / Q000188:drug therapy*; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology / Q000627:therapeutic use; D017998:Leukotriene D4 / Q000037:antagonists & inhibitors; D010982:Platelet-Derived Growth Factor / Q000037:antagonists & inhibitors; D011945:Receptors, Angiotensin / Q000378:metabolism; D011960:Receptors, Estrogen / Q000819:agonists
D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors; D002121:Calcium Channel Blockers; D004791:Enzyme Inhibitors; D007166:Immunosuppressive Agents; D010982:Platelet-Derived Growth Factor; D011945:Receptors, Angiotensin; D011960:Receptors, Estrogen; D000804:Angiotensin II; D017998:Leukotriene D4