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. 2014 Jul 20;8(2):101.
doi: 10.4172/1747-0862.1000101.

Balancing AhR-Dependent Pro-Oxidant and Nrf2-Responsive Anti-Oxidant Pathways in Age-Related Retinopathy: Is SERPINE1 Expression a Therapeutic Target in Disease Onset and Progression?

Paul J Higgins  1
Affiliations

Balancing AhR-Dependent Pro-Oxidant and Nrf2-Responsive Anti-Oxidant Pathways in Age-Related Retinopathy: Is SERPINE1 Expression a Therapeutic Target in Disease Onset and Progression?

Paul J Higgins. J Mol Genet Med. .
No abstract available

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Figures

Figure 1
Figure 1
Regulation of the proteolytic microenvironment. A highly-interactive plasmin-matrix metalloproteinase (MMP) pericellular proteolytic cascade is finely “titrated” both temporally and spatially by SERPINE1 (PAI-1). This complex cooperating system of proteases and inhibitors is fundamental to normal tissue repair and development of chronic diseases (adapted from [11]).
Figure 2
Figure 2
A model for ROS involvement in SERPINE1 induction by TGF-β1. TGF-β1 receptor activation upon ligand binding activates Smad 2/3 (via phosphorylation by the ALK5/TGF-β1 receptor 1 type) as well as non-Smad (e.g. EGFR, MAPK, Akt, Rho-ROCK) signaling cascades with downstream effects on gene expression (e.g. SERPINE1). Rapid ROS generation in response to TGF-β1 stimulation appears critical for initiation of non-SMAD (e.g. EGFR, SRC) pathways. p53 integrates transcriptional contributions from both SMAD and non-SMAD cascades, as well as with accessory cofactors (e.g., USF2), to attain maximal SERPINE1 expression (modified from [15]).
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