RNA-Seq transcriptomic landscape profiling of spontaneously hypertensive rats treated with a sodium-glucose cotransporter 2 (SGLT2) inhibitor
Abstract
BACKGROUND
Sodium-glucose co-transporter-2 inhibitor (SGLT2i) are antihyperglycemic medications that reduce cardiovascular disease (CVD) and improve chronic kidney disease prognosis in patients with diabetes mellitus. The specific impact of SGLT2i treatment on hypertensive individuals, however, remains to be established. This underscores the need for systematic efforts to profile the molecular landscape associated with SGLT2i administration.
METHODS
We conducted a detailed RNA-sequencing (RNA-Seq)-based exploration of transcriptomic changes in response to empagliflozin in eight different tissues (i.e., atrium, aorta, ventricle, white adipose, brown adipose, kidney, lung, and brain) from a male rat model of spontaneously hypertension. Corresponding computational analyses (i.e., clustering, differentially-expressed genes [DEG], and functional association) were performed to analyze these data. Blood pressure measurements, tissue staining studies and RT-qPCR were performed to validate our in silico findings.
RESULTS
We discovered that empagliflozin exerted potent transcriptomic effects on various tissues, most notably the kidney, white adipose, and lung in spontaneously hypertension rats (SHR). The functional enrichment of DEGs indicated that empagliflozin may regulate blood pressure, blood glucose and lipid homeostasis in SHR. Consistent with our RNA-Seq findings, immunohistochemistry and qPCR analyses revealed decreased renal expression of mitogen-activated protein kinase 10…
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