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Inhibition of HIF-prolyl hydroxylase promotes renal tubule regeneration via the reprogramming of renal proximal tubular cells.
Acta Pharmacol Sin
January 2025
Division of Nephrology, Nanfang Hospital, Southern Medical University; National Clinical Research Center for Kidney Disease; State Key Laboratory of Organ Failure Research; Guangdong Provincial Institute of Nephrology; Guangdong Provincial Key Laboratory of Renal Failure Research, Guangzhou, 510515, China.
The ability of the mammalian kidney to repair or regenerate after acute kidney injury (AKI) is very limited. The maladaptive repair of AKI promotes progression to chronic kidney disease (CKD). Therefore, new strategies to promote the repair/regeneration of injured renal tubules after AKI are urgently needed.
View Article and Find Full Text PDFAnemia is a major clinical manifestation seen in myelodysplastic syndromes (MDS). Treatment options for anemia in low-risk MDS are limited. Especially, oral medication which is uniformly effective for anemia in low-risk MDS is required.
View Article and Find Full Text PDFHypoxia-inducible factor activators: a novel class of oral drugs for the treatment of anemia of chronic kidney disease.
Hematology Am Soc Hematol Educ Program
December 2024
Medical and Research Service, Department of Veterans Affairs, Tennessee Valley Healthcare System, Nashville, TN.
Anemia is a hallmark of chronic kidney disease (CKD), worsens with disease progression, and profoundly affects a patient's well-being. Major pathogenic factors are inadequate kidney erythropoietin (EPO) production and absolute and functional iron deficiency. The 2 mainstays of current anemia treatment are a) replacement therapy with recombinant EPO or 1 of its glycosylated derivatives, administered subcutaneously or intravenously, and b) intravenous (IV) iron injections.
View Article and Find Full Text PDFPost-ischemic inactivation of HIF Prolyl Hydroxylases in endothelium promotes maladaptive kidney repair by inducing glycolysis.
J Clin Invest
November 2024
Division of Nephrology & Hypertension, Northwestern University Feinberg School of Medicine, Chicago, United States of America.
Article Synopsis
- Ischemic acute kidney injury (AKI) is a frequent issue for hospitalized patients and increases the risk of developing chronic kidney disease (CKD).
- The study identifies the importance of specific enzymes (PHD1, PHD2, and PHD3) in kidney repair after ischemia, revealing that altering these enzymes leads to worse kidney damage and inflammation.
- Inhibiting a protein called MCT4 can improve kidney repair by reducing inflammation and preventing damage caused by a faulty metabolic response in endothelial cells, suggesting a potential treatment strategy for preventing the progression from AKI to CKD.
Molecular exploration of natural and synthetic compounds databases for promising hypoxia inducible factor (HIF) Prolyl-4- hydroxylase domain (PHD) inhibitors using molecular simulation and free energy calculations.
BMC Chem
November 2024
School of Chemical Sciences, Universiti Sains Malaysia, 11800, Penang, Malaysia.
Article Synopsis
- Hypoxia-inducible factors (HIFs) play a crucial role in regulating erythropoietin synthesis and red blood cell production, with PHD enzymes being vital for controlling HIF stability and activity.
- The study identified potential PHD inhibitors from over 13,000 compounds using molecular docking and dynamics simulations, revealing four promising candidates that bind more effectively to PHD2 than the existing drug, Vadadustat.
- Among the candidates, ZINC36378940 emerged as the most promising with the strongest binding affinity, suggesting it should be further explored for therapeutic applications.
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