NOX4 and hydronephrosis: SERCA2a is responsible for refilling calcium into the sarcoplasmic reticulum during the diastolic phase of a heart cycle, and decreased SERCA2a expression results in diastolic dysfunction.[19] In addition, in the animal model, increased TGF-β levels activate the phosphorylation of Smad2, which upregulates Nox4-based NADPH oxidase and causes SERCA oxidation and dysfunction.[20] These results suggest that elevated TGF-β causes diastolic dysfunction in the scenarios of ureteral obstruction and hydronephrosis.