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BACKGROUND: Various renal abnormalities, including hydronephrosis, polycystic kidney disease, and hydroureter, have been reported, and these abnormalities are present in DiGeorge syndrome, renal dysplasia, and acute kidney failure. Previous studies have shown that various genes are associated with renal abnormalities. However, the major target genes of nonobstructive hydronephrosis have not yet been elucidated. RESULTS: We examined neuroblast differentiation-associated protein Ahnak localization and analyzed morphogenesis in developing kidney and ureter. To investigated function of Ahnak, RNA-sequencing and calcium imaging were performed in wild type and Ahnak knockout (KO) mice. Ahnak localization was confirmed in the developing mouse kidneys and ureter. An imbalance of calcium homeostasis and hydronephrosis, which involves an expanded renal pelvis and hydroureter, was observed in Ahnak KO mice. Gene Ontology enrichment analysis on RNA-seq results indicated that 'Channel Activity', 'Passive Transmembrane Transporter Activity' and 'Cellular Calcium Ion Homeostasis' were downregulated in Ahnak KO kidney. 'Muscle Tissue Development', 'Muscle Contraction', and 'Cellular Calcium Ion Homeostasis' were downregulated in Ahnak KO ureter. Moreover, peristaltic movement of smooth muscle in the ureter was reduced in Ahnak KO mice. CONCLUSIONS: Abnormal calcium homeostasis causes renal disease and is regulated by calcium channels. In this study, we focused on Ahnak, which regulates calcium homeostasis in several organs. Our results indicate that Ahnak plays a pivotal role in kidney and ureter development, and in maintaining the function of the urinary system.
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Objective: To explore the mechanism of Salvia miltiorrhiza in treatment of microcirculatory disturbance based on network pharmacology. Methods: The targets of S. miltiorrhiza’s active components for treatment of microcirculatory disturbance were screened and predicted by utilizing TCMSP, PubChem Search, Genecards database and Swiss target prediction online tool. Cytoscape 3.3.0 software was adopted to construct an active component-microcirculatory disturbance target network. The protein-protein interaction (PPI) network was established by using STRING database. DAVID database was used to analyze metabolism pathway in target gene ontology (GO) biological process, Kyoto encyclopedia of genes and gnomes (KEGG). Results: Totally 65 active components of S. miltiorrhiza and nine related targets were screened. GO and KEGG pathway enrichment analysis revealed that active components of S. miltiorrhiza participated in oxidation-reduction process, cellular calcium ion homeostasis and other biological processes, and S. miltiorrhiza may regulate VEGF signaling pathway, cholinergic synapse signal transduction, oxytocin signaling pathway, aldosterone-regulated sodium reabsorption pathway and so on. Conclusion: This study reflects the characteristics of multi-components, multi-targets, and multi-pathways of S. miltiorrhiza in the treatment of microcirculation disturbance, which may provide new ideas and methodology for further research on the treatment of microcirculatory disturbance using S. miltiorrhiza.