The unexpected interplay between the stem cell factor Lin28 and inflammation response

Lin28 is a stem cell factor which is mainly expressed in stem and progenitor cells and undergoes a significant downregulation during cell differentiation. Ectopic expression of Lin28 is associated with abnormal development, cell transformation and tumor formation. We previously found that specific Lin28 expression in the nephrons results in the formation of cystic kidneys.

To explore the mechanism by which Lin28 expression leads to kidney damage we performed global gene expression analysis by RNA seq. Strikingly, this analysis revealed a very strong inflammation response in the transgenic kidneys. We validated that there is indeed an inflammation response in the kidneys by blood tests, FACS analysis, ELISA and H&E staining. This inflammation response didn’t appear in any other organ that we analyzed. Moreover, Lin28 over-expression in the stromal cells of the kidney didn’t lead to inflammation. Therefore, we concluded that the inflammation is a local response that occurs upon Lin28 expression in specific cell types. Finally, our preliminary results suggest that the inflammation is the cause of the cystic kidney phenotype and not its result.

Overall, these findings are the first demonstration of in-vivo inflammation response as a result of Lin28 overexpression. While Lin28 has been studied so far in the context of stem cells and tumor development, this study suggests that ectopic expression of Lin28 might play a role also in inflammation development. Unraveling this surprising effect of Lin28 ectopic expression may shed a new light on the link between inflammation and cancer.