Autophagy Regulates Formation of Primary Cilia in Mefloquine-Treated Cells

Primary cilia have critical roles in coordinating multiple cellular signaling pathways. Dysregulation of primary cilia is implicated in various ciliopathies. To identify specific regulators of autophagy, we screened chemical libraries and identified mefloquine, an anti-malaria medicine, as a potent regulator of primary cilia in human retinal pigmented epithelial (RPE) cells. Not only ciliated cells but also primary cilium length was increased in mefloquine-treated RPE cells. Treatment with mefloquine strongly induced the elongation of primary cilia by blocking disassembly of primary cilium. In addition, we found that autophagy was increased in mefloquine-treated cells by enhancing autophagic flux. Both chemical and genetic inhibition of autophagy suppressed ciliogenesis in mefloquine-treated RPE cells. Taken together, these results suggest that autophagy induced by mefloquine positively regulates the elongation of primary cilia in RPE cells.

Changes of Bone Mineral Densities in Children with Idiopathic Hypercalciuria / 대한신장학회지

PURPOSE: Idiopathic hypercalciuria is a common clinical disorder in children with hematuria or nephrolithiasis. Recently, it has been reported that idiopathic hypercalciuria may disturb the metabolism of bone and induce its loss. We measured the biochemical markers of bone metabolism and bone mineral densities (BMD) by dual energy X-ray absorptiometry (DEXA) in children with idiopathic hypercalciuria to elucidate the prevalence and clinical significance of osteopenia. METHODS: From 1997 to 2005, 52 children with idiopathic hypercalciuria were included in this study. The biochemical markers of bone metabolism were measured in all 52 patients. BMD was measured in 21 patients initially and additional 6 patients during the follow-up. RESULTS: Mean age of patients was 6 years 7 months, and the male to female ratio was 1.26:1. BMD Z-scores were less than -1 in 10 of initial 21 patients (osteopenia), and -2.5 in 2 of 10 osteopenic patients (osteoporosis). There was a negative correlation between BMD Z-score and the level of osteocalcin. However, there were no significant differences in BMD Z-scores and other biochemical markers of bone metabolism among groups divided by sex, the type of idiopathic hypercalciuria, and the presence of urinary stone. CONCLUSION: Idiopathic hypercalciuria can be not only the cause of hematuria, but also of osteopenia in children. We suggest that the measurement of BMD in children with idiopathic hypercalciuria should be performed routinely with regular follow-up.