Robert Tanguay, Ph.D.
Oregon State University
P42ES016465, R21ES025421, T32ES07060, F31ES026518, P30ES000210
NIEHS grantees found a new gene in zebrafish that could lead to a better understanding of how exposure to chemicals leads to disease in humans. The study describes the interactions between chemicals that can activate the aryl hydrocarbon receptor (AHR), which is a protein involved in regulating a number of biological responses, and the newly discovered gene, known as slincR. A variety of chemicals, including dioxins and polycyclic aromatic hydrocarbons (PAHs), can activate AHR, contributing to adverse health effects in humans and wildlife. In zebrafish, an important gene in human development, sox9b, is repressed in several AHR-mediated toxic responses, including developmental malformations.
In the study, researchers demonstrated that slincR represses sox9b in response to dioxin exposure. They also found that slincR expression may play a causal role in dioxin-induced developmental effects and can regulate cartilage development. In addition, slincR expression was significantly increased by exposure to a number of environmentally relevant PAHs.
The study team identified genes in humans and mice that perform the same function as slincR, supporting the human health relevance of the model. According to the authors, these data improve what we know about AHR activation by environmental pollutants and may be used to predict the types of compounds that will react with the AHR receptor.
Citation: Garcia GR, Shankar P, Dunham CL, Garcia A, La Du JK, Truong L, Tilton SC, Tanguay RL. 2018. Signaling events downstream of AHR activation that contribute to toxic responses: the functional role of an AHR-dependent long noncoding RNA (slincR) using the zebrafish model. Environ Health Perspect 126(11):117002.