|Glucotoxicity: IGT postprandial, IFG, and overt T2DM||
Protein Kinase C (PKC) activation.|
Altered integrin expression of podocyte and pericyte: (podocyte-pericyte loss)
|Increased Synthesis Of: Type Iv Collagen||TGF beta, VEGF, and possibly PDGF beta 1. All associated with PKC activation and induction of growth hormones – factors from glucotoxicity and → ROS.|
Increased Maintenance of: type IV Collagen|
AGE cross-linking of type IV collagen.
AGE – RAGE connection.
|Increased resistance to protease (MMP) degradation, allowing type IV collagen to accumulate.|
|Decreased Degradation.||Decreased MMP-2 MMP-3|
|Decreased Degradation.||Increased expression of TIMP-2|
In general, ROS promotes ECM fibrosis under the influence of chronic injurious stimuli and is associated with the chronic inflammatory state.
increases all aspects of type IV accumulation: Glucotoxicity → PKC activation, AGE cross-linking activation, Decreased eNOS and eNO activity resulting in increased MMP activation.*