Indispensable role of factor for adipocyte differentiation 104 (fad104) in lung maturation.

Factor for adipocyte differentiation 104 (fad104) is a regulator of adipogenesis and osteogenesis. Our previous study showed that fad104-deficient mice died immediately after birth, suggesting fad104 to be essential for neonatal survival. However, the cause of this rapid death is unclear. Here, we demonstrate the role of fad104 in neonatal survival. Phenotypic and morphological analyses showed that fad104-deficient mice died due to cyanosis-associated lung dysplasia including atelectasis. Furthermore, immunohistochemistry revealed that FAD104 was strongly expressed in ATII cells in the developing lung. Most importantly, the ATII cells in lungs were immature, and impaired the expression of surfactant-associated proteins. Collectively, these results indicate that fad104 has an indispensable role in lung maturation, especially the maturation and differentiation of ATII cells.

Differential localizations of the transient receptor potential channels TRPV4 and TRPV1 in the mouse urinary bladder.

We studied the localization and physiological functions of the transient receptor potential (TRP) channels TRPV1 (TRP vanilloid 1) and TRPV4 (TRP vanilloid 4) in the mouse bladder, because both channels are thought to be mechanosensors for bladder distention. RT-PCR specifically amplified TRPV4 transcripts from the urothelial cells, whereas TRPV1 transcripts were barely detectable. ISH experiments showed that TRPV4 transcripts were abundantly expressed in the urothelium, whereas TRPV1 transcripts were not detectable in the urothelial cells. Immunoblotting and IHC studies showed that TRPV4 proteins were mainly localized at the basal plasma membrane domains of the basal urothelial cells. In contrast, TRPV1-immunoreactivities were found not in the urothelial cells but in the nerve fibers that innervate the urinary bladder. In Ca(2+)-imaging experiments, 4alpha-phorbol 12,13-didecanoate, a TRPV4 agonist, and hypotonic stimuli induced significant increases in intracellular calcium ion concentration ([Ca(2+)](i)) in isolated urothelial cells, whereas capsaicin, a TRPV1 agonist, showed no marked effect on the cells. These findings raise the possibility that, in mouse urothelial cells, TRPV4 may contribute to the detection of increases in intravesical pressure related to the micturition reflex.

Acid-sensing ion channel-1b in the stereocilia of mammalian cochlear hair cells.

We investigated whether amiloride-blockable proton-gated cation channels ASIC1a (acid-sensing ion channel-1a) and ASIC1b are expressed in the stereocilia of mouse cochlear hair cells. In-situ hybridization studies showed that ASIC1b transcripts, but not ASIC1a transcripts, were expressed in the inner and outer hair cells. Fluorescent immunohistochemical and immunogold electron microscopic analyses revealed that the ASIC1b channels were located at the insertions of the stereocilia into the hair cells. Our findings provide a novel molecular key to the understanding of cochlear physiology and pathophysiology.