PUBLICATION
Establishment of a Ciliogenesis-Associated Signaling Model for Polycystic Kidney Disease
- Authors
- Lu, L., Liu, Q., Zhi, L., Che, X., Xiao, B., Cui, M., Yu, M., Yang, B., Zhang, J., Zhang, B.
- ID
- ZDB-PUB-210902-8
- Date
- 2021
- Source
- Kidney & blood pressure research 46(6): 693-701 (Journal)
- Registered Authors
- Keywords
- GNAS, Phosphatidylinositol 4 kinase III-β, Polycystic kidney disease, Primary cilia
- MeSH Terms
-
- Cell Line
- Cilia/genetics*
- Cilia/metabolism
- Cilia/pathology
- Gene Regulatory Networks*
- Humans
- Polycystic Kidney Diseases/genetics*
- Polycystic Kidney Diseases/metabolism
- Polycystic Kidney Diseases/pathology
- Protein Interaction Maps
- Signal Transduction
- Transcriptome
- PubMed
- 34469896 Full text @ Kidney Blood Press. Res.
Citation
Lu, L., Liu, Q., Zhi, L., Che, X., Xiao, B., Cui, M., Yu, M., Yang, B., Zhang, J., Zhang, B. (2021) Establishment of a Ciliogenesis-Associated Signaling Model for Polycystic Kidney Disease. Kidney & blood pressure research. 46(6):693-701.
Abstract
Background Polycystic kidney disease (PKD) represents the most prevalent inherited progressive kidney disorder in humans. Due to complexity of the genetic network behind the disease, the molecular mechanisms of PKD are still poorly understood yet.
Objectives This study aimed to develop a ciliogenesis-associated gene network for PKD patients and comprehensively understand the molecular mechanisms underlying the disease.
Method The potential hub genes were selected based on the differential expression analysis from the GEO database. Meanwhile, the primary hub genes were further elucidated by both in vivo and in vitro experiments.
Results In this study, we established a comprehensive differentially expressed genes profile (including GNAS, PI4KB, UMOD, SLC7A13, and MIOX) for PKD patients compared with the control specimen. At the same time, enrichment analysis was utilized to demonstrate that the G-protein-related signaling and cilia assembling signaling pathways were closely associated with PKD development. The further investigations of the interaction between 2 genes (GNAS and PI4KB) with in vivo and in vitro analyses revealed that PI4KB functioned as a downstream factor for GNAS and spontaneously activated the phosphorylation of Akt into p-Akt for ciliogenesis in PKD formation. The PI4KB depletion mutant zebrafish model displayed a PKD phenotype as well as absence of primary cilia in the kidney.
Conclusions Collectively, our work discovered an innovative potential signaling pathway model for PKD formation, which provided a valuable insight for future study of the mechanism of this disease.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping