• Korean Journal of Veterinary Research
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• v.36 no.4
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• pp.747-755
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• 1996

The regional distribution and relative frequencies of the gastro-entero-pancreatic endocrine cells were studied immunohistochemically in the GIT and pancreas of the Korean mole. Seven kinds of endocrine cells were identified in this study. Although 5-HT- and somatostatin-immunoreactive cells were seen throughout the GIT, they were most predominant in the pyloric gland region. Glucagon-immunoreactive cells were restricted on the large intestine. Bovine CG-immunoreactive cells were more frequent in the stomach than in the intestines which were not detected in the duodenum. Numerous Gas/CCK-immunoreactive cells were found in the pyloric gland region, but rarely in the jejunum and ileum. BPP-immunoreactive cells were observed to be rare in the stomach and ileum but were a few in number in the intestines. In the pancreas, four types, namely, glucagon-, somatostatin-, BPP- and insulin-immunoreactive cells were identified in the pancreatic islets and exocrine portion. These results suggest that although endocrine cells of the Korean mole is less abundant in the duodenum, the distribution pattern of its gastro-entero-pancreatic endocrine cells is similar to that reported for the Korean hedgehog.

• Development and Reproduction
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• v.25 no.4
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• pp.279-291
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• 2021

Hair loss is one of the most common chronic diseases, with a detrimental effect on a patient's psychosocial life. Hair loss results from damage to the hair follicle (HF) and/or hair regeneration cycle. Various damaging factors, such as hereditary, inflammation, and aging, impair hair regeneration by inhibiting the activation of hair follicle stem cells (HFSCs) and dermal papilla cells (DPCs). Formyl peptide receptor 2 (FPR2) regulates the inflammatory response and the activity of various types of stem cells, and has recently been reported to have a protective effect on hair loss. Given that stem cell activity is the driving force for hair regeneration, we hypothesized that FPR2 influences hair regeneration by mediating HFSC activity. To prove this hypothesis, we investigated the role of FPR2 in hair regeneration using Fpr2 knockout (KO) mice. Fpr2 KO mice were found to have excessive hair loss and abnormal HF structures and skin layer construction compared to wild-type (WT) mice. The levels of Sonic hedgehog (Shh) and β-catenin, which promote HF regeneration, were significantly decreased, and the expression of bone morphogenetic protein (Bmp)2/4, an inhibitor of the anagen phase, was significantly increased in Fpr2 KO mice compared to WT mice. The proliferation of HFSCs and DPCs was significantly lower in Fpr2 KO mice than in WT mice. These findings demonstrate that FPR2 impacts signaling molecules that regulate HF regeneration, and is involved in the proliferation of HFSCs and DPCs, exerting a protective effect on hair loss.

• Molecules and Cells
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• v.42 no.9
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• pp.661-671
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• 2019

Adipose tissue-derived mesenchymal stem cells (ADSCs) are promising for regenerating degenerated intervertebral discs (IVDs), but the low efficiency of nucleus pulposus (NP)-specific differentiation limits their clinical applications. The Sonic hedgehog (Shh) signaling pathway is important in NP-specific differentiation of ADSCs, and Smoothened Agonist (SAG) is a highly specific and effective agonist of Shh signaling. In this study, we proposed a new differentiation strategy with the use of the small molecule SAG. The NP-specific differentiation and extracellular matrix (ECM) synthesis of ADSCs were measured in vitro, and the regenerative effects of SAG pretreated ADSCs in degenerated IVDs were verified in vivo. The results showed that the combination of SAG and transforming growth factor-${\beta}3$ ($TGF-{\beta}3$) is able to increase the ECM synthesis of ADSCs. In addition, the gene and protein expression levels of NP-specific markers were increased by treatment with SAG and $TGF-{\beta}3$. Furthermore, SAG pretreated ADSCs can also improve the disc height, water content, ECM content, and structure of degenerated IVDs in vivo. Our new differentiation scheme has high efficiency in inducing NP-specific differentiation of ADSCs and is promising for stem cell-based treatment of degenerated IVDs.

• Asian-Australasian Journal of Animal Sciences
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• v.32 no.3
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• pp.341-349
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• 2019

Objective: Internal organs indirectly affect economic performance and well-being of animals. Study of internal organs during later layer period will allow full utilization of layer hens. Hence, we conducted a genome-wide association study (GWAS) to identify potential quantitative trait loci or genes that potentially contribute to internal organ weight. Methods: A total of 1,512 chickens originating from White Leghorn and Dongxiang Blue-Shelled chickens were genotyped using high-density Affymetrix 600 K single nucleotide polymorphism (SNP) array. We conducted a GWAS, linkage disequilibrium analysis, and heritability estimated based on SNP information by using GEMMA, Haploview and GCTA software. Results: Our results displayed that internal organ weights show moderate to high (0.283 to 0.640) heritability. Variance partitioned across chromosomes and chromosome lengths had a linear relationship for liver weight and gizzard weight ($R^2=0.493$, 0.753). A total of 23 highly significant SNPs that associated with all internal organ weights were mainly located on Gallus gallus autosome (GGA) 1 and GGA4. Six SNPs on GGA2 affected heart weight. After the final analysis, five top SNPs were in or near genes 5-Hydroxytryptamine receptor 2A, general transcription factor IIF polypeptide 2, WD repeat and FYVE domain containing 2, non-SMC condensin I complex subunit G, and sonic hedgehog, which were considered as candidate genes having a pervasive role in internal organ weights. Conclusion: Our findings provide an understanding of the underlying genetic architecture of internal organs and are beneficial in the selection of chickens.

• Journal of Genetic Medicine
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• v.18 no.1
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• pp.64-69
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• 2021

Primary cilium has a signal transduction function that is essential for brain development, and also determines cell polarity and acts as a mediator for important signaling systems, especially the Sonic Hedgehog (SHH) pathway. TBC1D32 is a ciliary protein, implicated in SHH signaling. Biallelic mutations in the TBC1D32 gene causes a kind of ciliopathy, heterogeneous developmental or degenerative disorders that affect multiple organs, including the brain. Here we report a boy who carried compound heterozygous variants in TBC1D32. The patient showed hypotonia, respiratory difficulty, and multiple anomalies at his birth. He was diagnosed with congenital hypopituitarism and treated with T4, hydrocortisone, and growth hormone. Despite the hormonal replacement, the patient needed long-term respiratory support with tracheostomy and nutritional support with a feeding tube. His developmental milestones were severely retarded. Hydrocephalus and strabismus developed and both required surgery, during the outpatient follow-up. Whole-exome sequencing indicated compound heterozygous variants, c.2200C>T (p.Arg734^*) and c.156-1G>T, in TBC1D32 gene. This is the first Korean case of TBC1D32-related ciliopathy and we reported detailed and sequential clinical features. This case demonstrated the utility of whole-exome sequencing and provided valuable clinical data on ultra-rare disease.

• KSBB Journal
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• v.20 no.5 s.94
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• pp.363-370
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• 2005

Neural stem cells (NSCs) of the central nervous system (CNS) have raised a great interest not only for their importance in basic neural development but also for their therapeutic potentials in neurologically degenerative diseases such as Parkinson's, Alzheimer and stroke. During the CNS development, two molecular cascades determine specification of midbrain dopamine system. In one pathway, FGF-8, sonic hedgehog and transcription factor Nurr1 specify dopamine neurotransmitter phenotype. In the other, transcription factors $Lm{\times}lb\;and\;Pt{\times}3$ are required for induction of dopaminergic neurons. In Nurr1 knockout mouse, tyrosine hydroxylase (TH) positive cells fail to appear in substantia nigra, indicating that Nurr1 is essential in specification of dopaminergic cell phenotype. In this study, we used the immortalized human NSCs retrovirally transduced with Nurr1 gene to probe the Nurr1 mediated mechanism to induce dopamine phenotype. While Nurr1 over-expression alone did not generate dopamine phenotype in NSCs, applications of retinoid and forskolin induced expression of TH and AADC mRNAs. In addition, co-cultures of Nurr1 expressing NSCs with human astrocytes induced a marked increase of TH expression. In this co-culture system, the addition of retinoid and forskolin dramatically increased expression of TH. These results indicate that the immortalized human NSCs with Nurr1 gene could have a clinical utility for cell replacement for the Parkinson patients.

• The Korean Journal of Zoology
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• v.31 no.2
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• pp.111-121
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• 1988

This study was attempted to investigate the regional distribution and shapes of pancreatic endocrifle cells in the hedgehog, Erinaceus koneanus by the immunocytochemical PAP methods (Nalane, 1968; Stemberger, 1979). The tissue specimen taken from the splenic and duodenal regions of pancreas(proximai, middle and distal portions, respectively) were fixed with Bouin solution and the sections(5$\mu$ m) were followed by simple and double staining with 2 substrates, DAB and 4-CI-1-naphthol. The results were as following: Glucagon(A) cells, 13 $\mu$ m x 9.5 $\mu$ m in size, were found in the islets periphery and among the exocrine parenchyma. A cells were abundant in all the portions of splenic region and distal portion of duodenal region in contrast to a few in the proximal and middle portion of duodenal region. The shapes of the A cells were round, oval and pyramidal types. Insulin(B) cells, 11.6$\mu$m x 9.4$\mu$m in sise, were round or oval in shape and located throughout the islets. B cells were the most numerous cell types in all portions of splenic region and distal protion of duodenal region as compared with the other portions. Somatostatin(D) cells, 12.6$\mu$m x 9.1 $\mu$m in size, were round or oval in shape and found in the islets periphery and scattered in the exocrine parenchyma. These cells were rare in all the portions of splenic and duodenal region. Pancreatic polypeptide(PP) cells of various type, 12.8$\mu$ m x 8.5 $\mu$ m in size, were found in the islets periphery and among the exocrine parenchyma. PP cells were numerous in the proximal and middle portion of duodenal region, but rarely scattered in the other portions.

• Journal of Applied Biological Chemistry
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• v.64 no.4
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• pp.421-431
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• 2021

It has been suggested that some toothpastes have the potential to promote hair growth. However, there was no scientific verification on the hair growth effect of toothpaste and no scientific report on major active ingredients in toothpaste. In this work, toothpaste and its constituents were applied topically over the shaved skin of C57BL/6 mice and evaluated. Results indicated that toothpaste showed hair growth effect. Also, the effect of toothpaste constituents on the proliferation rate of keratinocyte cells was investigated. The mixture solution of 𝛼-tocopherol acetate, l-menthol, and stevioside, each of that was known to promote hair growth and other toothpaste constituents were applied topically on mouse skin. When the mixture solution was included, hair growth effect was observed in mice. Transcriptome analysis was performed using the dorsal epidermis of mice from the group treated with toothpaste, the mixture which are presumed to be active ingredients for hair growth, and from mice used for the control group. As a result of analyzing the genes whose expression was significantly changed in each treatment group, the gene patterns of the two groups were very similar. Also, when functional genomic analysis was performed, genes with functions related to hair growth regulation showed a high extent of the change in both groups. Hair growth-related genes whose expression was changed in both groups included keratin, keratin-related proteins, forkhead box, and sonic hedgehog. Therefore, the hair growth effect of toothpaste is thought to be due to the effect of a mixture of 𝛼-tocopherol acetate, l-menthol, and stevioside.

• Journal of the Korean Society of Environmental Restoration Technology
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• v.9 no.3
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• pp.51-58
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• 2006

The purpose of this research presents a method to position and makes the structure for eco-corridors reasonably with collectable analysing results of various effects shown in mammals' road-kill at 429 points. Target animals of this research are Leopard cat, Siberian weasel, Raccoon dog, Korean hare, Eurasian red squirrel, Siberian chipmunk and Water deer. The results derived from the empirical analysis on the contents above are followed. First, according to the results as for Leopard cat road kill analysis, which is designated as Endangered Species Class II, the eco-corridor might be located at near village having stead food in order to decrease the frequencies of road-kill, because its road kill points were mainly collected at 4 lane hilly road with mountain-road-farm area geological type of. Second, because Siberian weasel's road kill was detected at 2 lane hilly road with mountain-road-stream geological type, the eco-corridor might be located at near a mill to decrease road-kill frequencies. Third, the road-kill frequency of Eurasian red squirrel can be reduced when the eco-corridor is located at the area across coniferous tree near 4 lane west sea freeway with mountain-road-mountain. Fourth, the road-kill of Raccoon dog can be reduced when the eco-corridor is located at 4 lane mountain road or hilly road with the geological type having farm land-road-mountain(stream). Fifth, Korean hare's road-kill can be reduced when the eco-corridor is located at grass land across ridge line of mountain, because wild rabbit road kill was happened at 4 lane mountain road or 2 lane mountain road(mountain-road-mountain). Sixth, As for Siberian chipmunk, the eco-corridor might be located at the side slope of mountain road at 2 lane mountain road under the speed of 60km/h with mountain-road-mountain. Seventh, For Water deer, the eco-corridor might be located at 4 lane hilly road with mountain-road-farm land. As for Common otter, Amur hedgehog, Yellow-throated marten, Weasel, it is difficult to specify the proper site of eco-corridor due to the lack of data. Eco-corridors for carnivores might be well located at 4 lane hilly road or 2 lane hilly road with mountain-road-farm land, and the track for herbivores might be well located as a overhead bridge on mountain-road-mountain type across mountains. In order to position eco-corridors for wildlife properly, we have to research animal's behavior with ecological background, and to consider the local uniqueness and regularly collect the empirical road-kill data in long term 3 to 5 year, which can be the foundation for the more suitable place of wild life eco-corridors.

• Molecules and Cells
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• v.37 no.7
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• pp.547-553
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• 2014

Glioblastoma multiforme (GBM) is one of the most common brain malignancies and has a very poor prognosis. Recent evidence suggests that the presence of cancer stem cells (CSC) in GBM and the rare CSC subpopulation that is resistant to chemotherapy may be responsible for the treatment failure and unfavorable prognosis of GBM. A garlic-derived compound, Z-ajoene, has shown a range of biological activities, including anti-proliferative effects on several cancers. Here, we demonstrated for the first time that Z-ajoene specifically inhibits the growth of the GBM CSC population. CSC sphere-forming inhibition was achieved at a concentration that did not exhibit a cytotoxic effect in regular cell culture conditions. The specificity of this inhibitory effect on the CSC population was confirmed by detecting CSC cell surface marker CD133 expression and biochemical marker ALDH activity. In addition, stem cell-related mRNA profiling and real-time PCR revealed the differential expression of CSC-specific genes, including Notch, Wnt, and Hedgehog, upon treatment with Z-ajoene. A proteomic approach, i.e., reverse-phase protein array (RPPA) and Western blot analysis, showed decreased SMAD4, p-AKT, 14.3.3 and FOXO3A expression. The protein interaction map (http://string-db.org/) of the identified molecules suggested that the AKT, ERK/p38 and $TGF{\beta}$ signaling pathways are key mediators of Z-ajoene's action, which affects the transcriptional network that includes FOXO3A. These biological and bioinformatic analyses collectively demonstrate that Z-ajoene is a potential candidate for the treatment of GBM by specifically targeting GBM CSCs. We also show how this systemic approach strengthens the identification of new therapeutic agents that target CSCs.