Matches in SemOpenAlex for { <https://semopenalex.org/work/W4223569383> ?p ?o ?g. }
- W4223569383 endingPage "558.e13" @default.
- W4223569383 startingPage "545" @default.
- W4223569383 abstract "Zebrafish and mammalian neonates possess robust cardiac regeneration via the induction of endogenous cardiomyocyte (CM) proliferation, but adult mammalian hearts have very limited regenerative potential. Developing small molecules for inducing adult mammalian heart regeneration has had limited success. We report a chemical cocktail of five small molecules (5SM) that promote adult CM proliferation and heart regeneration. A high-content chemical screen, along with an algorithm-aided prediction of small-molecule interactions, identified 5SM that efficiently induced CM cell cycle re-entry and cytokinesis. Intraperitoneal delivery of 5SM reversed the loss of heart function, induced CM proliferation, and decreased cardiac fibrosis after rat myocardial infarction. Mechanistically, 5SM potentially targets α1 adrenergic receptor, JAK1, DYRKs, PTEN, and MCT1 and is connected to lactate-LacRS2 signaling, leading to CM metabolic switching toward glycolysis/biosynthesis and CM de-differentiation before entering the cell-cycle. Our work sheds lights on the understanding CM regenerative mechanisms and opens therapeutic avenues for repairing the heart." @default.
- W4223569383 created "2022-04-15" @default.
- W4223569383 creator A5000868352 @default.
- W4223569383 creator A5001691024 @default.
- W4223569383 creator A5006378344 @default.
- W4223569383 creator A5013577819 @default.
- W4223569383 creator A5014095048 @default.
- W4223569383 creator A5014586870 @default.
- W4223569383 creator A5017825677 @default.
- W4223569383 creator A5020085314 @default.
- W4223569383 creator A5020188195 @default.
- W4223569383 creator A5020309893 @default.
- W4223569383 creator A5028351634 @default.
- W4223569383 creator A5031259664 @default.
- W4223569383 creator A5031603333 @default.
- W4223569383 creator A5032678723 @default.
- W4223569383 creator A5049833213 @default.
- W4223569383 creator A5050986709 @default.
- W4223569383 creator A5053533157 @default.
- W4223569383 creator A5054894456 @default.
- W4223569383 creator A5054938468 @default.
- W4223569383 creator A5059081976 @default.
- W4223569383 creator A5060744228 @default.
- W4223569383 creator A5062253569 @default.
- W4223569383 creator A5065284134 @default.
- W4223569383 creator A5077558876 @default.
- W4223569383 creator A5077601351 @default.
- W4223569383 creator A5082706176 @default.
- W4223569383 creator A5083037234 @default.
- W4223569383 creator A5086520847 @default.
- W4223569383 date "2022-04-01" @default.
- W4223569383 modified "2023-10-16" @default.
- W4223569383 title "A small-molecule cocktail promotes mammalian cardiomyocyte proliferation and heart regeneration" @default.
- W4223569383 cites W140226651 @default.
- W4223569383 cites W1480171680 @default.
- W4223569383 cites W1615535881 @default.
- W4223569383 cites W1969038150 @default.
- W4223569383 cites W1969210272 @default.
- W4223569383 cites W1996435746 @default.
- W4223569383 cites W2010368308 @default.
- W4223569383 cites W2035618305 @default.
- W4223569383 cites W2054604628 @default.
- W4223569383 cites W2068018422 @default.
- W4223569383 cites W2070734183 @default.
- W4223569383 cites W2071765960 @default.
- W4223569383 cites W2073999055 @default.
- W4223569383 cites W2078215784 @default.
- W4223569383 cites W2082714048 @default.
- W4223569383 cites W2086294280 @default.
- W4223569383 cites W2093494581 @default.
- W4223569383 cites W2095059099 @default.
- W4223569383 cites W2101986300 @default.
- W4223569383 cites W2103441770 @default.
- W4223569383 cites W2103807671 @default.
- W4223569383 cites W2104005232 @default.
- W4223569383 cites W2117577687 @default.
- W4223569383 cites W2126747203 @default.
- W4223569383 cites W2139689863 @default.
- W4223569383 cites W2147987903 @default.
- W4223569383 cites W2151395497 @default.
- W4223569383 cites W2154152918 @default.
- W4223569383 cites W2156140279 @default.
- W4223569383 cites W2157671340 @default.
- W4223569383 cites W2158170306 @default.
- W4223569383 cites W2160734881 @default.
- W4223569383 cites W2160785529 @default.
- W4223569383 cites W2167279371 @default.
- W4223569383 cites W2171808845 @default.
- W4223569383 cites W2179438025 @default.
- W4223569383 cites W2231291760 @default.
- W4223569383 cites W2254879660 @default.
- W4223569383 cites W2327474899 @default.
- W4223569383 cites W2508395040 @default.
- W4223569383 cites W2528173482 @default.
- W4223569383 cites W2560514568 @default.
- W4223569383 cites W2593601792 @default.
- W4223569383 cites W2620870293 @default.
- W4223569383 cites W2621046444 @default.
- W4223569383 cites W2623156160 @default.
- W4223569383 cites W2625547916 @default.
- W4223569383 cites W2790882351 @default.
- W4223569383 cites W2794480084 @default.
- W4223569383 cites W2886893896 @default.
- W4223569383 cites W2896000464 @default.
- W4223569383 cites W2899305057 @default.
- W4223569383 cites W2912091946 @default.
- W4223569383 cites W2916020270 @default.
- W4223569383 cites W2928068407 @default.
- W4223569383 cites W2936738922 @default.
- W4223569383 cites W2939862834 @default.
- W4223569383 cites W2943870140 @default.
- W4223569383 cites W2947470310 @default.
- W4223569383 cites W2957016747 @default.
- W4223569383 cites W2964849163 @default.
- W4223569383 cites W2988246256 @default.
- W4223569383 cites W2990139677 @default.
- W4223569383 cites W2995700709 @default.
- W4223569383 cites W2998087297 @default.