![]() Involvement of PAI-1 in renal metabolic alterations has not been well characterized. PAI-1 expression is robustly induced in renal tubules and interstitial cells during various nephropathies, including obstructive uropathy, in both humans and mice. This is orchestrated by three enzymes that catalyze irreversible steps in the pathway: hexokinase-1 (HK-1), phosphofructokinase-1 (PFK-1), and pyruvate kinase M2 (PKM2). Glycolysis is a multi-step reaction, which converts glucose to pyruvate, generating energy. ![]() While upstream controls are not fully elucidated, increased glycolysis has emerged as an important factor in obstructive nephropathies. Metabolic alterations were recently identified as a key contributor to the progression of fibrosis. PAI-1 is a causative factor in the progression of obstructive uropathy to CKD, but the pathophysiological basis is not well understood. ![]() Some patients with obstructive uropathy develop fibrosis and chronic kidney disease (CKD), which affects more than 850 million people worldwide.
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