People with acne will find this JCI paper of interest. 13-cis retinoic acid can be used to treat acne, as it can kill human sebaceous-gland cells by apoptosis. The molecule is teratogenic, though, making it necessary to look for alternatives. As the mechanism of action of 13-cis retinoic acid is unknown, Amanda Nelson and her colleagues tried to elucidate it, hoping to identify new targets for the treatment of the bothersome skin condition. Using transcriptional profiling of skin cells from people with acne and cultured sebaceous glands, they found that lipocalin-2 was distinctively upregulated by treatment with 13-cis retinoic acid. They also found that the apoptotic effect of 13-cis retinoic acid indeed depended on the expression of neutrophil gelatinase–associated lipocalin (NGAL), the protein encoded by lipocalin-2; by using siRNA to lipocalin-2, they blocked the apoptotic effect, and by adding recombinant NGAL, they promoted it. It is therefore conceivable that manipulating NGAL expression could lead to a new way to fight acne.
A more serious pathology with a connection to retinoids is Matthew-Wood syndrome, a fatal disease characterized by multisystem developmental malformations that has been linked to mutations in STRA6. STRA6 interacts with retinol-binding protein 4 (RBP4), which is, in turn, a carrier of retinoids (vitamin A and its derivatives). A paper published in Cell Metabolism establishes that the biochemical interaction between STRA6 and RBP4 is indeed functionally relevant. Studying zebrafish embryos, Andrea Isken and colleagues found that Stra6 deficiency allows more Rbp4 to remain free and to carry an excess amount of retinoids to several embryonic tissues, including bone, heart and eye. In fact, reducing the levels of Rbp4 prevented these effects. The findings provide a nice molecular account of Matthew-Wood syndrome, although I cannot help but wish that the authors had done the in vivo experiments in a mammal. I must confess that, when we evaluate papers at Nature Medicine, we’re seldom enthused by data from zebrafish, Drosophila or C. elegans, as the relevance of these models to human physiology tends to be harder to ascertain. Nothing personal against the fish or the invertebrates, though.