Abstract

Family with sequence similarity 13 member A (FAM13A) has been associated with several chronic lung diseases and has a strong genetic link to COPD. While extensive genomic studies have been performed, the biological role of FAM13A protein is still not completely elucidated.

A major challenge for understanding the role of FAM13A in disease is its complex transcript landscape with multiple isoforms. There is little insight into which isoforms are expressed in different cell types and whether the expression is altered in COPD.

The human full length FAM13A protein possesses a RhoGAP domain with unclear function. Whilst a high expression of full-length FAM13A was observed in fully differentiated air-liquid interphase (ALI) cultures of primary bronchial epithelial cells, very low to undetectable levels were detected in submerged cell culture conditions. Using qPCR together with western blot we observe the induction of full length FAM13A during the in vitro differentiation of epithelial cells which coincide with the appearance of ciliated cells.

In order to investigate the role of FAM13A in human primary lung epithelial cells, we generated and profiled several FAM13A specific antisense oligonucleotides (ASOs). The FAM13A specific ASOs dose-dependently decreased expression of FAM13A in fully differentiated ALI cultures but had no effect on ciliary function. In contrast, knocking down FAM13A during the differentiation of lung epithelial cells led to a very clear and dramatic decrease in cilia formation and function.Our data fits well with the hypothesis that FAM13A has a protective role in lung epithelia and suggests that full length FAM13A has a crucial role in developing functional cilia.