Lithium Modulates Cilia Length in Renal Collecting Duct Cells

Abstract

Cilia are important regulators of multiple cell processes throughout the body. Optimal cellular function can depend on cell‐specific regulation of cilia length; however, the mechanisms that control cilia length are not well understood. Defects in ciliary length appear to be related to ciliopathic diseases, which often present with renal cysts. Lithium chloride (LiCl) has been shown to affect cilia in multiple cell types, but its effects have not been explored in inner medullary collecting duct (IMCD) cells. We found that following a 24 hr LiCl (25 mM) treatment of IMCD cells in vitro, cilia are significantly elongated by 1.5 fold. Although LiCl can inhibit GSK3β, addition of the GSK3β‐specific inhibitor TDZD‐8 did not increase IMCD cilia length, indicating that LiCl‐mediated cilia elongation is independent of GSK3β. Instead we found that the SQ‐22536‐inhibtion of adenylate cyclases in IMCD cells mimics LiCl‐mediated cilia elongation, whereas addition of a cAMP analog in the presence of LiCl presence prevents elongation. In addition, we observed a similar increase in cilia length in renal collecting duct cells from rats fed dietary lithium for 2 wk coinciding with a decrease in urinary cAMP. We conclude that lithium increases cilia length in IMCD cells by dampening cellular cAMP in a manner independent of GSK3β. Our data provide new insights into the effects of LiCl on renal cilia and suggest that lithium may have therapeutic benefits in the treatment of some ciliopathies.Support or Funding InformationEmory SOM‐Renal Division