title: Hyperglycemia and glucosamine-induced mesangial cell cycle arrest and hypertrophy: Common or independent mechanisms?
abstract: The Hexosamine Pathway (HP) is one hypothesis proposed to explain glucose toxicity and the alterations observed during the course of diabetic microvascular complication development. Glucosamine is a precursor of UDP-N-Acetylglucosamine (UDP-GlcNAc), the main product of the HP that has often been used to mimic its activation. The transfer of a UDP-GlcNAc residue onto proteins (O-GlcNAc modification) represents the final step of the HP and is considered as a major mechanism by which this pathway exerts its signalling effects. While it is well accepted that the HP promotes extracellular matrix accumulation in the context of diabetic nephropathy, its involvement in the perturbations of cell cycle progression and hypertrophy of renal cells has been poorly investigated. Nevertheless, in a growing number of studies, the HP and O-GlcNAc modification are emerging as important regulators of cell cycle progression. This review will focus on the role of glucosamine and O-GlcNAc modification in cell cycle regulation in the context of diabetic nephropathy. Special emphasis will be given into the role of the HP as a potential mediator of the effects of high glucose on the perturbations of renal cell growth.
authors.affiliation: Diabetic Microangiopathy Research Unit, Merck-Santé/INSERM UMR 585, INSA-Lyon, Villeurbanne, France.
authors.forename: Elodie
authors.initials: E
authors.lastname: Masson
authors.forename: Michel
authors.initials: M
authors.lastname: Lagarde
authors.forename: Nicolas
authors.initials: N
authors.lastname: Wiernsperger
authors.forename: Samer
authors.initials: S
authors.lastname: El Bawab
mesh_terms: D000818:Animals; D002453:Cell Cycle / Q000502:physiology*; D005944:Glucosamine / Q000502:physiology*; D006801:Humans; D006943:Hyperglycemia / Q000378:metabolism*; D006984:Hypertrophy / Q000378:metabolism / Q000473:pathology; D050527:Mesangial Cells / Q000166:cytology / Q000473:pathology / Q000502:physiology*
chemical_list: D005944:Glucosamine