Primary Cilia as a Signaling Platform for Control of Energy Metabolism

Obesity has become a common healthcare problem worldwide. Cilia are tiny hair-like organelles on the cell surface that are generated and anchored by the basal body. Non-motile primary cilia have been considered to be evolutionary rudiments until a few decades, but they are now considered as important signaling organelles because many receptors, channels, and signaling molecules are highly expressed in primary cilia. A potential role of primary cilia in metabolic regulation and body weight maintenance has been suspected based on rare genetic disorders termed as ciliopathy, such as Bardet-Biedl syndrome and Alström syndrome, which manifest as obesity. Recent studies have demonstrated involvement of cilia-related cellular signaling pathways in transducing metabolic information in hypothalamic neurons and in determining cellular fate during adipose tissue development. In this review, we summarize the current knowledge about cilia and cilia-associated signaling pathways in the regulation of body metabolism.

Expression of sonic hedgehog in adult rat models of acute compressive spinal cord injury / 中国组织工程研究

BACKGROUND:In the development of nervous system, the main effect of sonic hedgehog signaling pathway is to induce the partition of dorsal and ventral sides in the central nervous system. When above signaling pathway is destroyed, ventral neurons in the central nervous system wil completely lose. OBJECTIVE: To establish adult rat models of acute compressive spinal cord injury, to detect the expression of development-related sonic hedgehog after acute compressive spinal cord injury, and to explore its effects on neural regeneration. METHODS:A total of 30 Sprague-Dawley rats at the same age were placed in a posterior compression device to establish models of acute compressive spinal cord injury. They were then randomly divided into lamina driling group (n=5) and acute spinal cord injury group (n=25). Sonic hedgehog mRNA was detected by in situ hybridization method at the injury site at 1, 3, 5, 7, and 14 days after spinal cord. RESULTS AND CONCLUSION:The expression levels of sonic hedgehog increased to the maximal expression levels in grey and white matters 10 mm distal to the lesion site at 7 days after injury. Sonic hedgehog expression was apparently less in ependymal cels than in grey and white matters and was restricted to 5 mm distal to the lesion site, being narrower in its distribution than its occurrence in grey and white matters. These data indicated that acute compressive spinal cord injury can induce the expression of sonic hedgehog. This expression maybe relates to adult neural cel regeneration.

Possible Role of Sonic Hedgehog and Epithelial-Mesenchymal Transition in Renal Cell Cancer Progression

PURPOSE: Sonic hedgehog (Shh) signaling and epithelial-mesenchymal transition (EMT) are both known to relate to cancer progression. The purpose of this study was to investigate the role of Shh signaling and EMT in renal cell carcinoma (RCC). MATERIALS AND METHODS: Cell proliferation was assayed in RCC cell lines in the presence or absence of a Shh signaling stimulator, recombinant Shh (r-Shh) protein, or a Shh signaling inhibitor, cyclopamine. Real-time reverse transcription-polymerase chain reaction (RT-PCR) was performed to study the expression of EMT markers (E-cadherin, N-cadherin, and vimentin) and osteonectin. The expression of Ki-67, Gli-1, osteonectin, and EMT markers in nephrectomy specimens from RCC patients was also measured by immunohistochemical (IHC) staining. RESULTS: RCC cells showed enhanced cell proliferation by r-Shh protein, whereas cell proliferation was suppressed by the addition of cyclopamine in RenCa cells. Real-time RT-PCR showed that r-Shh suppressed the expression of E-cadherin and that this suppression was partly blocked by cyclopamine alone in RenCa cells. In the IHC results, osteonectin significantly correlated with vein sinus invasion (p=0.0218), and the expression of vimentin significantly correlated with lymphatic invasion (p=0.0392). CONCLUSIONS: Shh signaling and EMT play roles in RCC progression, and the Shh signaling inhibitor cyclopamine might be a possible molecular targeted therapeutic strategy for RCC.

Recurrence of Colorectal Neoplasm Cannot Be Predicted by Sonic Hedgehog Expression in the Normal Colonic Tissue

BACKGROUND/AIMS: The expression of sonic hedgehog (Shh) in the colon cancer cell has been implicated in colorectal carcinogenesis. However, the association between Shh expression in the normal colonic mucosa and the recurrence of colorectal neoplasm after tumor resection has not been well documented. The aim of the study was to determine the association between Shh expression in the normal colonic mucosa and in the recurrence of colorectal neoplasm. METHODS: Fifty-five patients who underwent a long-term follow-up colonoscopy after the colorectal neoplasm resection were included. At the time of the tumor resection, Shh expression in the normal colonic mucosa was examined. The association between Shh expression in the normal colonic mucosa and the recurrence of colorectal neoplasm was analyzed. RESULTS: In total, 97 colorectal neoplasms were detected among 41 subjects after a mean follow-up period of 63 weeks (range 27-254 weeks). Of 55 subjects, 26 (47.3%) exhibited positive Shh expression in the normal colonic tissue, and the recurrence rate did not differ with the degree of Shh expression (P=0.238). The degree of Shh expression was not associated with the number (P=0.389), size (P=0.928), location (P=0.410), pathologic types (P=0.127), or time of recurrence (P=0.711) of the recurred colorectal neoplasm. CONCLUSIONS: Most colorectal neoplasm patients show recurrence after the resection and exhibit Shh expression in the normal colonic tissue. The degree of Shh expression in the normal colonic mucosa does not predict the recurrence of colorectal neoplasm.

An Outbreak of Caparinia tripilis in a Colony of African Pygmy Hedgehogs (Atelerix albiventris) from Korea

In February 2010, dermatitis characterized by scale and self-trauma due to puritis was recognized in a group of 22 four-toed hedgehogs (Atelerix albiventris Wagner, 1841) from a local pet shop in Gwangju, Korea. Microscopic examinations of skin scraping samples showed numerous mites of all developmental stages. Morphologically, pedicels of adult mites were short and unjointed. Tarsal caruncles were bell-shaped on all legs of males while they were absent on legs III and IV of females. Three long setae on the third pair of legs in both sexes were present. Adult males had posterior end of the abdomen with trilobate projection on each side, each lobe with a long seta. Based on these features, the mites were identified as Caparinia tripilis. This is the first report of caparinic mite infestation in hedgehogs from Korea. Identification keys for the family Psoroptidae and the genus Caparinia are provided.

Expression of hedgehog signaling pathway in squamous cell carcinoma / 中华皮肤科杂志

Objective To investigate the expression of Ptch-1 and Gli-1, hedgehog pathway-related genes in squamous cell carcinoma (SCC), and the effect of cyclopamine, a specific inhibitor of hedgehog signaling pathway, on the proliferation of a SCC cell line Tca. Methods Skin samples were resected from 42 patients with SCC and 10 normal human controls. Immunohistochemistry and in situ hybridization were employed to study the expression and distribution of Ptch-1 and Gli-1 in these specimens. Tca cells were incubated with cyclopamine (1, 2, 5, 10 μmol/mL) for 48 hours, or cyclopamine (5 μmol/mL) for 1-8 days. The same concentrations of lycopersicin served as the control treatment. Then, MTT assay was performed to detect the proliferation of Tca cells. A fraction of Tca cells were cultured in the presence of 5 μmol/mL cyclopamine for 72 hours followed by BrdU assay for the evaluation of cell growth and proliferation. Results A significant increment was shown in the expression of both Patch-1 and Gli-1 by immunohistochemistry (χ2= 5.656, 6.732, P<0.05, 0.01, respectively) and in situ hybridization (χ2=6.787, 9.600, respectively, both P<0.01) in SCC tissue compared with the control specimens. And both of them were predominantly distributed in the cytoplasm of SCC cells. As MTT assay revealed, cyclopamine notably inhibited the proliferation of Tea cells, and the effect increased with the concentration and action time of cyclopamine. Further more, the percentage of BrdU-positive cells was 26% in cyclopamine-treated Tca cells, significantly higher than that in the blank control cells (77%) and lycopersicin-treated cellls (72%). Conclusions Hedgehog signaling pathway is activated in the lesions of SCC, and inhibition of the pathway may facilitate the treatment of SCC.

A Case of Trychophyton mentagrophytes var. erinacei Infection from a Patient's Pet Hedgehog / 대한의진균학회지

Hedgehogs are nocturnal spiny mammals in a rodent family. Recently in Korea, the more hedgehogs are raised in the house as pets, the more people are acquired various infections from them. Herein, we report a case of Trichophyton(T.) mentagrophytes var. erinacei infection transmitted from the patient's pet hedgehog. The patient was a 37-year-old man who raised a hedgehog for 6 months. He presented with scaly, erythematous papules and plaques on the left hand and right elbow for 3 months. Potassium hydroxide (KOH) examination, fungus culture and PCR for the fungal strain showed T. mentagrophytes var. erinacei. Treatment was performed systemically and topically with antifungal agents and skin lesions were improved without recurrence. Up to date, there have been only three case-reports of T. mentagrophytes var. erinacei infection transmitted from pet hedgehogs in the English literature. Here we report a rare and interesting case.