Polycystic diseases in visceral organs

Abstract

Primary cilia are nonmotile, microtubule-based, antenna-like organelles projecting from the apical surface of most mammalian cells. Elegant studies have established the importance of ciliary structure and function in signal transduction and the sensory roles of cilia in maintaining healthy cellular state. In particular, dysfunctional cilia have been implicated in a large number of diseases mainly characterized by the presence of fluid-filled cysts in various organs. Aside from polycystic kidney disease (PKD), however, the roles of cilia in polycystic liver disease (PLD), polycystic pancreas disease (PPD), and polycystic ovarian syndrome (PCOS) are still very vague. In addition, although gender and sex hormones are known to regulate cyst formation, their roles in regulating physiological functions of cilia need to be further explored.

Figure 1

Primary cilia are present in vivo and in vitro. Primary cilia are present in all vestibular organs or tissues with vestibules (canals) that support perfusion of bodily fluid. Shown here are representative images demonstrating the presence of primary cilia in endothelial cells. (a) Scanning electron micrograph shows the presence of primary cilia in the lumen of mouse femoral artery. (b) Immunofluorescence image verify the presence of cilia in the mouse femoral endothelia. (c) When these endothelial cells were isolated, the cells retained their cilia in culture, as depicted in the image. Blue denotes cell nuclei; green represents acetylated-α-tubulin used as a cilia marker; red indicates actin cytoskeleton.

Figure 2

Mechanosensory cilia function involves calcium signal transduction. Mechanosensory cilia require functional polycystin complex. Fluid-flow-induced cilia bending will activate polycystin complex. This will mobilize calcium ions (Ca²⁺) influx from the extracellular matrix (ECM) into the cell. Calcium-induced calcium release will further activate various calcium-dependent proteins to maintain proper organogenesis.

Figure 3

Defects in planar cell polarity results in cystogenesis. It is hypothesized that normal cilia function is required to control proper directional cell division. (a) Normal directional cell division is required to have an elongated tubular formation. (b) Disrupted directional cell division results in expanded formation of tubule.