Moh'd Mohanad Al-Dabet, Khurrum Shahzad, Ahmed Elwakiel, Alba Sulaj, Stefan Kopf, Fabian Bock, Ihsan Gadi, Silke Zimmermann, Rajiv Rana, Shruthi Krishnan, Dheerendra Gupta, Jayakumar Manoharan, Sameen Fatima, Sumra Nazir, Constantin Schwab, Ronny Baber, Markus Scholz, Robert Geffers, Peter Rene Mertens, Peter P Nawroth, John H Griffin, Maria Keller, Chris Dockendorff, Shrey Kohli, Berend Isermann
A major obstacle in diabetes is the metabolic or hyperglycemic memory, which lacks specific therapies. Here we show that glucose-mediated changes in gene expression largely persist in diabetic kidney disease (DKD) despite reversing hyperglycemia. The senescence-associated cyclin-dependent kinase inhibitor p21 (Cdkn1a) was the top hit among genes persistently induced by hyperglycemia and was associated with induction of the p53-p21 pathway. Persistent p21 induction was confirmed in various animal models, human samples and in vitro models...
August 27, 2022: Nature Communications