Proximal tubular epithelia-specific transcriptomics of diabetic mice treated with dapagliflozin

The importance of proinflammatory failed-repair tubular epithelia as a predictor of diabetic kidney disease progression

“…In the early diabetic kidney, because of an increase in sodium reabsorption through SGLT2, the tissue hypoxic region expands toward the kidney cortex. 10 , 13 , 40 , 41 , 42 Advanced DKD contains the combined pathophysiologies of CKD and DKD; therefore, renal cortical tissue hypoxia was more evident in our novel advanced DKD mouse model than in Nx- db/m mice and non-Nx db/db mice. A recent study on the single cell-based transcriptomics of diabetic kidneys demonstrated that a hypoxic response was enhanced in the proximal tubules of the diabetic kidney, and an SGLT2 inhibitor reduced this signaling response.…”

“… 1 , 2 , 3 , 4 , 5 , 6 , 7 Experimental investigations have offered various mechanistic insights into the renoprotective effects of SGLT2 inhibitors for early DKD through blood glucose lowering-dependent and -independent pathways, 8 such as reductions in oxidative stress, 9 , 10 improvements in glomerular hyperfiltration, 10 , 11 energy utilization by ketone body production, 12 and tissue hypoxia. 10 , 13 We and other researchers demonstrated that SGLT2 inhibitors attenuated decreases in tissue oxygen tension in the early diabetic kidney, which was attributed to the inhibition of sodium reabsorption reducing energy requirements through basolateral Na-K ATPase. 10 , 13 , 14 , 15 …”

“… 10 , 13 We and other researchers demonstrated that SGLT2 inhibitors attenuated decreases in tissue oxygen tension in the early diabetic kidney, which was attributed to the inhibition of sodium reabsorption reducing energy requirements through basolateral Na-K ATPase. 10 , 13 , 14 , 15 …”

“…Tissue hypoxia was visualized and quantified. 10 , 13 , 42 In detail, Two hours before sacrifice, luseogliflozin or vehicle was administered to mice by oral gavage. One hour later, pimonidazole (HypoxyprobeTM-1, Natural Pharmacia International, Inc., Burlington, MA) in saline was intraperitoneally injected at a dose of 60 mg/kg.…”