• Korean Journal of Bronchoesophagology
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• v.5 no.1
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• pp.42-48
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• 1999

Background： This study was undertaken to detect the patterns of ciliogenesis in newborn rats trachea. Materials and Methods： The experimental animals(Sprague-Dawley strain) were divided five groups, one day, two day, three day, five day and seven day newborns as experimental groups. To obtain differential distribution of $\alpha$-tubulins in the ciliated cells and patterns of ciliogenesis, we used immunohistochemical stain method with mouse anti $\alpha$-tubulin monoclonal antibody as the primary antibody and gold particles conjugated goat anti mouse IgG as the secondary antibody. And we observed the specimens by electron microscope (Hitach-600 Model). Results : 1) The distribution of the $\alpha$ -tubulin reactions in apical zone was slightly decreased from three day after birth. 2) From 5th day after birth, the decreasing number of gold particles in intermediate zone was remarkable. 3) On the comparison with the other zones, the number of gold particles in the Golgi zone for seven days showed no statistical difference. Conclusion : The ciliogenesis of the tracheal ciliated cells in early newborn rat were made via centriolar and acentriolar pathways, in late groups, from five day after birth, the major ciliogenesis pattern might be centriolar pathway.

• BMB Reports
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• v.52 no.10
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• pp.619-624
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• 2019

The primary cilium is a microtubule-based structure projecting from a cell. Although the primary cilium shows no motility, it can recognize environmental stimuli. Thus, ciliary defects cause severe abnormalities called ciliopathies. Ciliogenesis is a very complex process and involves a myriad of components and regulators. In order to excavate the novel positive regulators of ciliogenesis, we performed mRNA microarray using starved NIH/3T3 cells. We selected 62 murine genes with corresponding human orthologs, with significantly upregulated expression at 24 h after serum withdrawal. Finally, calpain-6 was selected as a positive regulator of ciliogenesis. We found that calpain-6 deficiency reduced the percentage of ciliated cells and impaired sonic hedgehog signaling. It has been speculated that this defect might be associated with decreased levels of ${\alpha}-tubulin$ acetylation at lysine 40. This is the first study to report a novel role of calpain-6 in the formation of primary cilia.

• BMB Reports
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• v.53 no.7
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• pp.367-372
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• 2020

Cell cycle-related kinase (CCRK) has a conserved role in ciliogenesis, and Ccrk defects in mice lead to developmental defects, including exencephaly, preaxial polydactyly, skeletal abnormalities, retinal degeneration, and polycystic kidney. Here, we found that Ccrk is highly expressed in mouse trachea and bronchioles. Ccrk mutants exhibited pulmonary hypoplasia and abnormal branching morphogenesis in respiratory organ development. Furthermore, we demonstrated that Ccrk mutant lungs exhibit not only impaired branching morphogenesis but also a significant sacculation deficiency in alveoli associated with reduced epithelial progenitor cell proliferation. In pseudoglandular stages, Ccrk mutant lungs showed a downregulation of Hedgehog (Hh) signaling and defects in cilia morphology and frequency during progenitor-cell proliferation. Interestingly, we observed that activation of the Hh signaling pathway by small-molecule smoothened agonist (SAG) partially rescued bud morphology during branch bifurcation in explants from Ccrk mutant lungs. Therefore, CCRK properly regulates respiratory airway architecture in part through Hh-signal transduction and ciliogenesis.

• Biomolecules & Therapeutics
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• v.30 no.2
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• pp.170-178
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• 2022

The airway epithelium is equipped with the ability to resist respiratory disease development and airway damage, including the migration of airway epithelial cells and the activation of TLR3, which recognizes double-stranded (ds) RNA. Primary cilia on airway epithelial cells are involved in the cell cycle and cell differentiation and repair. In this study, we used Beas-2B human bronchial epithelial cells to investigate the effects of the TLR3 agonist polyinosinic:polycytidylic acid [Poly(I:C)] on airway cell migration and primary cilia (PC) formation. PC formation increased in cells incubated under serum deprivation. Migration was faster in Beas-2B cells pretreated with Poly(I:C) than in control cells, as judged by a wound healing assay, single-cell path tracking, and a Transwell migration assay. No changes in cell migration were observed when the cells were incubated in conditioned medium from Poly(I:C)-treated cells. PC formation was enhanced by Poly(I:C) treatment, but was reduced when the cells were exposed to the ciliogenesis inhibitor ciliobrevin A (CilioA). The inhibition of Beas-2B cell migration by CilioA was also assessed and a slight decrease in ciliogenesis was detected in SARS-CoV-2 spike protein (SP)-treated Beas-2B cells overexpressing ACE2 compared to control cells. Cell migration was decreased by SP but restored by Poly(I:C) treatment. Taken together, our results demonstrate that impaired migration by SP-treated cells can be attenuated by Poly(I:C) treatment, thus increasing airway cell migration through the regulation of ciliogenesis.

• Journal of the Society of Cosmetic Scientists of Korea
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• v.44 no.1
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• pp.73-79
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• 2018

The primary cilium protrudes from the cell body like a bio-antenna that has many receptors, channels and signaling molecules to sense and response to external stimuli. The external environment such as ultraviolet irradiation, temperature, humidity, gravity and shear stress always influences skin. Skin responds to external stimuli and differentiates by making melanin, collagen and horny layer. Ciliogenesis participates in developmental processes of skin, such as keratinocyte differentiation and hair formation. And it was reported that skin pigmentation was inhibited when ciliogenesis was induced by sonic hedgehog-smoothened-GLI2 signaling. When skin is exposed to ultraviolet irradiation, alpha-melanocyte stimulating hormones (${\alpha}$-MSH) increase melanin synthesis through activation of the cAMP pathway in melanocytes. We observed that ${\alpha}$-MSH and cAMP production inducers inhibited ciliogenesis of melanocytes. Therefore, we thought that regulation of ciliogenesis is potential candidate target for the development of agents to treat undesirable hyperpigmentation of skin. As a result, we found out that an ethanol extract of Glycyrrhiza glabra (EGG) root and 3,4,5-trimethoxy cinnamate thymol ester (TCTE, Melasolv) significantly inhibit melanin synthesis of normal human melanocyte by inducing primary cilium formation. This study proposed new theory to regulate skin pigmentation and cosmetic components for skin whitening.

• BMB Reports
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• v.45 no.8
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• pp.427-432
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• 2012

Primary cilia, single hair-like appendage on the surface of the most mammalian cells, were once considered to be vestigial cellular organelles for a past century because of their tiny structure and unknown function. Although they lack ancestral motility function of cilia or flagella, they share common ground with multiciliated motile cilia and flagella on internal structure such as microtubule based nine outer doublets nucleated from the base of mother centrioles called basal body. Making cilia, ciliogenesis, in cells depends on the cell cycle stage due to reuse of centrioles for cell division forming mitotic spindle pole (M phase) and assembling cilia from basal body (starting G1 phase and maintaining most of interphase). Ciliary assembly required two conflicting processes such as assembly and disassembly and balance between these two processes determines the length of cilia. Both process required highly conserved transport system to supply needed substance to grow tip of cilia and bring ciliary turnover product back to the base of cilia using motor protein, kinesin and dynein, and transport protein complex, IFT particles. Disruption of ciliary structure or function causes multiple human disorder called ciliopathies affecting disease of diverse ciliated tissues ranging from eye, kidney, respiratory tract and brain. Recent explosion of research on the primary cilia and their involvement on animal development and disease attracts scientific interest on how extensively the function of cilia related to specific cell physiology and signaling pathway. In this review, I introduce general features of primary cilia and recent progress in understanding of the ciliary length control and signaling pathways transduced through primary cilia in vertebrates.

• BMB Reports
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• v.48 no.7
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• pp.380-387
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• 2015

Cilia are conserved subcellular organelles with diverse sensory and developmental roles. Recently, they have emerged as crucial organelles whose dysfunction causes a wide spectrum of disorders called ciliopathies. Recent studies on the pathological mechanisms underlying ciliopathies showed that the ciliary compartment is further divided into subdomains with specific roles in the biogenesis, maintenance and function of cilia. Several conserved sets of molecules that play specific roles in each subcompartment have been discovered. Here we review recent progress on our understanding of ciliary subcompartments, especially focusing on the molecules required for their structure and/or function. [BMB Reports 2015; 48(7): 380-387]

• Laboraroty Animal Research
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• v.34 no.4
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• pp.203-210
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• 2018

Stress severely disturbs physiological and mental homeostasis which includes adult neurogenesis in hippocampus. Neurogenesis in hippocampus is a key feature to adapt to environmental changes and highly regulated by multiple cellular signaling pathways. The primary cilium is a cellular organelle, which acts as a signaling center during development and neurogenesis in adult mice. However, it is not clear how the primary cilia are involved in the process of restraint (RST) stress response. Using a mouse model, we examined the role of primary cilia in repeated and acute RST stress response. Interestingly, RST stress increased the number of ciliated cells in the adult hippocampal dentate gyrus (DG). In our RST model, cell proliferation in the DG also increased in a time-dependent manner. Moreover, the analysis of ciliated cells in the hippocampal DG with cell type markers indicated that cells that were ciliated in response to acute RST stress are neurons. Taken together, these findings suggest that RST stress response is closely associated with an increase in the number of ciliated neurons and leads to an increase in cell proliferation.

• BMB Reports
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• v.48 no.12
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• pp.647-654
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• 2015

Energy homeostasis in our body system is maintained by balancing the intake and expenditure of energy. Excessive accumulation of fat by disrupting the balance system causes overweight and obesity, which are increasingly becoming global health concerns. Understanding the pathogenesis of obesity focused on studying the genes related to familial types of obesity. Recently, a rare human genetic disorder, ciliopathy, links the role for genes regulating structure and function of a cellular organelle, the primary cilium, to metabolic disorder, obesity and type II diabetes. Primary cilia are microtubule based hair-like membranous structures, lacking motility and functions such as sensing the environmental cues, and transducing extracellular signals within the cells. Interestingly, the subclass of ciliopathies, such as Bardet-Biedle and Alström syndrome, manifest obesity and type II diabetes in human and mouse model systems. Moreover, studies on genetic mouse model system indicate that more ciliary genes affect energy homeostasis through multiple regulatory steps such as central and peripheral actions of leptin and insulin. In this review, we discuss the latest findings in primary cilia and metabolic disorders, and propose the possible interaction between primary cilia and the leptin and insulin signal pathways which might enhance our understanding of the unambiguous link of a cell's antenna to obesity and type II diabetes.

• BMB Reports
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• v.46 no.2
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• pp.73-79
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• 2013

Polycystic kidney disease (PKD) is a common hereditary disorder which is characterized by fluid-filled cysts in the kidney. Mutation in either PKD1, encoding polycystin-1 (PC1), or PKD2, encoding polycystin-2 (PC2), are causative genes of PKD. Recent studies indicate that renal cilia, known as mechanosensors, detecting flow stimulation through renal tubules, have a critical function in maintaining homeostasis of renal epithelial cells. Because most proteins related to PKD are localized to renal cilia or have a function in ciliogenesis. PC1/PC2 heterodimer is localized to the cilia, playing a role in calcium channels. Also, disruptions of ciliary proteins, except for PC1 and PC2, could be involved in the induction of polycystic kidney disease. Based on these findings, various PKD mice models were produced to understand the roles of primary cilia defects in renal cyst formation. In this review, we will describe the general role of cilia in renal epithelial cells, and the relationship between ciliary defects and PKD. We also discuss mouse models of PKD related to ciliary defects based on recent studies.