Chronic fluid flow is an environmental modifier of renal epithelial function

Area of Science:

• Cell Biology
• Renal Physiology
• Biophysics

Background:

• Solitary or sensory cilia are ubiquitous cellular structures with largely unknown functions.
• Primary cilia are implicated in mechanosensation, responding to fluid flow with calcium influx and downstream signaling.
• Autosomal Dominant Polycystic Kidney Disease (ADPKD) is a common, progressive genetic disorder affecting kidney function.

Purpose of the Study:

• To investigate how fluid flow, acting through primary cilia, influences renal epithelial physiology during cell turnover.
• To determine the conditions under which fluid flow alters the function of renal epithelial tissue.

Main Methods:

• Utilized a wildtype renal epithelial cell line from the cortical collecting duct.
• Applied gentle orbital shaking to simulate physiologically relevant fluid flow.
• Measured transepithelial sodium current and performed immunostaining for mechanosensitive proteins and cytoskeletal components.

Main Results:

• Fluid flow significantly modifies transepithelial sodium current.
• Cell proliferation and the actin cytoskeleton are altered by fluid flow.
• Mechanosensitive proteins play a role in the cellular response to fluid flow.

Conclusions:

• Fluid flow directly impacts renal epithelial cell function, proliferation, and cytoskeletal organization via primary cilia.
• These findings enhance understanding of primary cilia mechanosensation.
• The study provides insights into the progression mechanisms of ADPKD.