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role of a small GTPase, RhoA, in skin inflammation

Final Report Summary - RHOA IN INFLAMMATION (role of a small GTPase, RhoA, in skin inflammation)

Rho A is a small GTPase with crucial functions in actin cytoskeleton organization in cultured cells. However, little is known about its role in a living organism. To understand RhoA function in skin development and skin diseases we generated mice with a keratinocyte specific deletion of the RhoA gene. We found unexpectedly that loss of RhoA does not result in any major changes of the actin cytoskeleton. However, it affects retinoic acid signaling in vivo and in primary keratinocytes in vitro. Eventually, we could describe a molecular mechanism linking RhoA function to retinoic acid metabolism. These results have been described in a manuscript that we currently prepare for re-submission.
Since retinoic acid signaling was shown to affect skin tumor formation, we tested skin tumor formation in mice with a keratinocyte-restricted deletion of the RhoA gene. Indeed, skin tumor formation was strongly altered. We currently investigate this phenotype further.
During the project period, Dr. Peyrollier contributed to 4 original publications and 1 review. The manuscript on the regulation of retinoic acid signaling by RhoA is considered to be her major publication. This documented scientific activity is believed to increase her chances to find a job in biomedical research.