TABLE 2.
Mediators regulate fibrosis through the STAT3 signaling pathway.
| Mediators | Models | Effects and related mechanisms | Reference |
|---|---|---|---|
| SHP-1 | SHP-1-overexpressing myocytes and fibroblasts | The use of STAT3 agonist colivelin leads to more ROS generation, ECM deposition, and TGF-β1/SMAD2 activation | Zang et al. (2023) |
| Hypoxia/reoxygenation induced cardiomyocytes | Y-box protein 1 knockdown attenuates acute myocardial infarction damage via SHP-1 mediated STAT3 suppression | Cao et al. (2020) | |
| PTEN | Coronary artery ischemia/reperfusion model in Type 1 diabetes rats induced by Streptozotocin | PTEN partially inhibits the post ischemic regulation and post hypoxic regulation of diabetes heart through destroying JAK2/STAT3 signaling pathway | Xue et al. (2016) |
| βIV spectrin | Cardiac specificity βIV spectrin KO mice | βIV spectrin deficiency in cardiomyocytes causes STAT3 impairment, fibrosis, and impaired cardiac function | Unudurthi et al. (2018) |
| Genetic and acquired mouse models of βIV-spectrin deficiency | βIV spectrin protein dysfunction leads to nuclear STAT3 accumulation and activation, which changes gene expression and CF behavior. Fibrosis and cardiac dysfunction in βIV spectrin-deficient mice are abolished by STAT3 inhibition | Patel et al. (2019) | |
| Elabela | Ang II induced myocardial hypertrophy and fibrosis exacerbation in hypertensive mice | By inhibiting the IL-6/STAT3/GPX4 signaling pathway, antagonize the promoting effects of Ang II mediated cardiac microvascular endothelial cells deionization, adverse myocardial remodeling, fibrosis, and cardiac dysfunction | Zhang et al. (2022b) |
| PPAR | Type 1 diabetes rat model induced by Streptozotocin | PPARδ activation might suppress STAT3 and lower connective tissue growth factor and Fibronectin levels in diabetic rats with cardiac fibrosis | Lo et al. (2017b) |
| PPARα knockout mice | PPARα blocks T helper 17 cell differentiation via IL-6/STAT3/RORγT pathway, thus alleviating autoimmune Myocarditis | Chang et al. (2019) | |
| SIRT3 | SIRT3 knockout mice | SIRT3 can inhibit the STAT3-NFATc2 signaling pathway, thereby reducing myofibroblast transdifferentiation and preventing cardiac fibrosis | Guo et al. (2017) |
Abbreviation: SHP-1, tyrosine phosphatase 1; ECM, extracellular matrix; ROS, active oxygen; TGF-β1, transforming growth factor-β1; SMAD2, small mother against decapentaplegic 2; PTEN, phosphatase and tensin homologue deleted on chromosome 10; CF, cardiac fibroblasts; GPX4, glutathione peroxidase; PPAR, peroxisome proliferator-activated receptor.