Environmental level bisphenol A accelerates alterations of the reno-cardiac axis by the MAPK cascades in male diabetic rats: An analysis based on transcriptomic profiling and bioinformatics

In humans and animal models, the kidneys and cardiovascular systems are negatively affected by BPA from the environment. It is considered that BPA have some potential estrogen-like and non-hormone-like properties. In this study, RNA-sequencing and its-related bioinformatics was used as the basic strategy to clarify the characteristic mechanisms of kidney–heart axis remodeling and dysfunction in diabetic male rats under BPA exposure. We found that continuous BPA exposure in diabetic rats aggravated renal impairment, and caused hemodynamic disorders and dysfunctions. There were 655 and 125 differentially expressed genes in the kidney and heart, respectively. For the kidneys, functional annotation and enrichment, and gene set enrichment analyses identified bile acid secretion related to lipid synthesis and transport, and MAPK cascade pathways. For the heart, these bioinformatics analyses clearly pointed to MAPKs pathways. A total of 12 genes and another total of 6 genes were identified from the kidney tissue and heart tissue, respectively. Western blotting showed that exposure to BPA activated MAPK cascades in both organs. In this study, the exacerbated remodeling of diabetic kidney–heart axis under BPA exposure and diabetes might occur through hemodynamics, metabolism disorders, and the immune-inflammatory response, as well as continuous estrogen-like stimulation, with focus on the MAPK cascades.