2013 B.S. Pharmacy, China Pharmaceutical University, China
All-trans-retinoic acid (ATRA), an active metabolite synthesized from oxidation of vitamin A, broadly controls the patterning of multiple vertebrate tissues during embryogenesis, including neural differentiation, body axis formation and organogenesis. But it’s also a potent teratogen, causing multi-organ birth defects in human, so the endogenous ATRA level must be tightly controlled. Our current study mainly focuses on short-chain dehydrogenase/ reductase superfamily member 3 (DHRS3), which is under the control of ATRA but can also carry out reduction of ATRA precursor, retinaldehyde, to retinol in NADPH-dependent manner as feedback to increased ATRA level. We hypothesized and now reach the conclusion that DHRS3 plays a physiologically important role as retinaldehyde reductase in vivo and prevents excess formation of ATRA, thereby exquisitely maintaining ATRA homeostasis and preventing developmental defects brought by altered ATRA metabolism. We are going to investigate the mechanism of regulation of DHRS3 and the negative feedback inhibition of DHRS3 on ATRA metabolism and signaling.