Pax6 co-expresses and gets compartmentalized in the heart of diabetic mice
Description
The Paired box (Pax6), a highly conserved transcription factor, and Tgf-β1 are involved in various cellular functions such as differentiation, activation of extracellular matrix proteins, epithelial-mesenchymal transition, production of cytokines, MAPK, NF-kB, PI3K, Tgf-βs, TLRs, and insulin signaling pathways. In the present study, it was observed that the epicardial, myocardial, and endocardial structures were distorted, and co-expression and compartmentalization of Pax6 and Tgf-β1 occurred in different layers of diabetic mice compared to the control. In the heart, Pax6 expression promotes cardiac fibroblast differentiation via maintaining Tgf-β1 levels. The Tgf-β1 is a pleiotropic cytokine involved in many biological functions. The ligand of Tgf-β1 and their signaling molecules are necessary for the heart's development and normal cardiovascular function. The high level of glucose stimulates Tgf-β1 dependent pathways and activates Tgf-β1 further leading to cardiac fibrosis which includes cardiac hypertrophy through SMAD-dependent and independent (canonical and non-canonical) pathways. Since expression of Tgf-β1 and Pax6 has been proven to be critical for the functional anatomy of the heart, Tgf-β1 and Pax6 might function like tissue-dependent regulation through various signaling pathways or networks. Results suggest that Tgf-β1 and Pax6 have a crucial role in the differentiation and development of cardiac fibroblasts and also regulate the differentiation of fibroblasts into myofibroblasts via SMAD-dependent and independent (canonical and non-canonical) pathways. However, the maintenance and differentiation of cardiac fibroblasts may lead to novel therapy in some patients with cardiac dysfunction.