Science. 2015 Jun 12;348(6240):aaa2340.
TISSUE REGENERATION. Inhibition of the prostaglandin-degrading enzyme 15-PGDH potentiates tissue regeneration.
Zhang Y1, Desai A1, Yang SY2, Bae KB3, et al.
Agents that promote tissue regeneration could be beneficial in a variety of clinical settings, such as stimulating recovery of the hematopoietic system after bone marrow transplantation. Prostaglandin PGE2, a lipid signaling molecule that supports expansion of several types of tissue stem cells, is a candidate therapeutic target for promoting tissue regeneration in vivo. Here, we show that inhibition of 15-hydroxyprostaglandin dehydrogenase (15-PGDH), a prostaglandin-degrading enzyme, potentiates tissue regeneration in multiple organs in mice. In a chemical screen, we identify a small-molecule inhibitor of 15-PGDH (SW033291) that increases prostaglandin PGE2 levels in bone marrow and other tissues. SW033291 accelerates hematopoietic recovery in mice receiving a bone marrow transplant. The same compound also promotes tissue regeneration in mouse models of colon and liver injury. Tissues from 15-PGDH knockout mice demonstrate similar increased regenerative capacity. Thus, 15-PGDH inhibition may be a valuable therapeutic strategy for tissue regeneration in diverse clinical contexts.
PMID: 26068857
Science. 2015 Jun 12;348(6240):1208-9.
Biomedicine. Bringing PGE₂ in from the cold.
FitzGerald GA1.
Prostaglandins (PGs) are evanescent, locally acting lipids. They are not stored within cells, but are generated when their precursor, arachidonic acid, is mobilized from cellular membranes by rather nonspecific activation of phospholipases. Most cells generate one or two dominant PGs, each with a remarkable diversity of effects. Prostaglandin E2 (PGE2) is a vasodilator that acts with other PGs and metabolic products of arachidonic acid to promote pain and inflammation. The development and clinical use of drugs that suppress the production of these PGs has been ongoing for decades, but PGE2 also has been long recognized to have a role in tissue maintenance and regeneration. Its stable analog, dimethyl PGE2, is currently being evaluated for use as an adjunct to hematopoietic stem cell transplantation. On page 1223 of this issue, Zhang et al. (1) report that elevating the capacity of tissues to form PGE2 by inhibiting 15-hydroxyprostaglandin dehydrogenase (15-PGDH), its major inactivating enzyme, augments the capacity for tissue regeneration in mouse models. So, is it time to bring PGE2, which we are so used to suppressing, in from the cold?
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TISSUE REGENERATION. Inhibition of the prostaglandin-degrading enzyme 15-PGDH potentiates tissue regeneration. [Science. 2015]
PMID: 26068834
