Person: Zhou, Jing
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Zhou
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Jing
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Zhou, Jing
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Publication The Cytoplasmic Tail of FPC Antagonizes the Full-Length Protein in the Regulation of mTOR Pathway(Public Library of Science, 2014) Wang, Shixuan; Wu, Maoqing; Yao, Gang; Zhang, Jingjing; Zhou, JingFPC (fibrocystin or polyductin) is a single transmembrane receptor-like protein, responsible for the human autosomal recessive polycystic kidney disease (ARPKD). It was recently proposed that FPC undergoes a Notch-like cleavage and subsequently the cleaved carboxy(C)-terminal fragment translocates to the nucleus. To study the functions of the isolated C-tail, we expressed the intracellular domain of human FPC (hICD) in renal epithelial cells. By 3-dimensional (3D) tubulogenesis assay, we found that in contrast to tubule-like structures formed from control cells, hICD-expressing cells exclusively formed cyst-like structures. By western blotting, we showed that the Akt/mTOR pathway, indicated by increased phosphorylation of Akt at serine 473 and S6 kinase 1 at threonine 389, was constitutively activated in hICD-expressing cells, similar to that in FPC knockdown cells and ARPKD kidneys. Moreover, application of mTOR inhibitor rapamycin reduced the size of the cyst-like structures formed by hICD-expressing cells. Application of either LY294002 or wortmannin inhibited the activation of both S6K1 and Akt. Expression of full-length FPC inhibited the activation of S6 and S6 kinase whereas co-expression of hICD with full-length FPC antagonized the inhibitory effect of full-length FPC on mTOR. Taken together, we propose that FPC modulates the PI3K/Akt/mTOR pathway and the cleaved C-tail regulates the function of the full-length protein.Publication Hair-Cell Mechanotransduction Persists in TRP Channel Knockout Mice(Public Library of Science, 2016) Wu, Xudong; Indzhykulian, Artur; Niksch, Paul; Webber, Roxanna M.; Garcia-Gonzalez, Miguel; Watnick, Terry; Zhou, Jing; Vollrath, Melissa A.; Corey, DavidMembers of the TRP superfamily of ion channels mediate mechanosensation in some organisms, and have been suggested as candidates for the mechanotransduction channel in vertebrate hair cells. Some TRP channels can be ruled out based on lack of an inner ear phenotype in knockout animals or pore properties not similar to the hair-cell channel. Such studies have excluded Trpv4, Trpa1, Trpml3, Trpm1, Trpm3, Trpc1, Trpc3, Trpc5, and Trpc6. However, others remain reasonable candidates. We used data from an RNA-seq analysis of gene expression in hair cells as well as data on TRP channel conductance to narrow the candidate group. We then characterized mice lacking functional Trpm2, Pkd2, Pkd2l1, Pkd2l2 and Pkd1l3, using scanning electron microscopy, auditory brainstem response, permeant dye accumulation, and single-cell electrophysiology. In all of these TRP-deficient mice, and in double and triple knockouts, mechanotransduction persisted. Together with published studies, these results argue against the participation of any of the 33 mouse TRP channels in hair cell transduction.Publication Inter-Study Variability in CMR Measurements of Right Ventricular Volume, Mass and Ejection Fraction in Tetralogy of Fallot: A Prospective Observational Study(BioMed Central, 2012) Blalock, Shannon E; Banka, Puja; Geva, Tal; Powell, Andrew; Zhou, Jing; Prakash, AshwinPublication Trends in Resource Utilization by Children with Neurological Impairment in the United States Inpatient Health Care System: A Repeat Cross-Sectional Study(Public Library of Science, 2012) Berry, Jay; Poduri, Annapurna; Bonkowsky, Joshua L.; Zhou, Jing; Graham, Dionne; Welch, Chelsea; Putney, Heather; Srivastava, RajenduJay Berry and colleagues report findings from an analysis of hospitalization data in the US, examining the proportion of inpatient resources attributable to care for children with neurological impairment.Publication Systems Biology Approach to Identify Transcriptome Reprogramming and Candidate MicroRNA Targets during the Progression of Polycystic Kidney Disease(BioMed Central, 2011) Pandey, Priyanka; Qin, Shan; Ho, Jacqueline; Zhou, Jing; Kreidberg, JordanBackground: Autosomal dominant polycystic kidney disease (ADPKD) is characterized by cyst formation throughout the kidney parenchyma. It is caused by mutations in either of two genes, \(PKD1\) and \(PKD2\). Mice that lack functional \(Pkd1 (Pkd1^{-/-})\), develop rapidly progressive cystic disease during embryogenesis, and serve as a model to study human ADPKD. Genome wide transcriptome reprogramming and the possible roles of micro-RNAs (miRNAs) that affect the initiation and progression of cyst formation in the \(Pkd1^{-/-}\) have yet to be studied. miRNAs are small, regulatory non-coding RNAs, implicated in a wide spectrum of biological processes. Their expression levels are altered in several diseases including kidney cancer, diabetic nephropathy and PKD. Results: We examined the molecular pathways that modulate renal cyst formation and growth in the \(Pkd1^{-/-}\) model by performing global gene-expression profiling in embryonic kidneys at days 14.5 and 17.5. Gene Ontology and gene set enrichment analysis were used to identify overrepresented signaling pathways in \(Pkd1^{-/-}\) kidneys. We found dysregulation of developmental, metabolic, and signaling pathways (e.g. Wnt, calcium, \(TGF-\beta\) and MAPK) in \(Pkd^{-/-}\) kidneys. Using a comparative transcriptomics approach, we determined similarities and differences with human ADPKD: ~50% overlap at the pathway level among the mis-regulated pathways was observed. By using computational approaches (TargetScan, miRanda, microT and miRDB), we then predicted miRNAs that were suggested to target the differentially expressed mRNAs. Differential expressions of 9 candidate miRNAs, miRs-10a, -30a-5p, -96, -126-5p, -182, -200a, -204, -429 and -488, and 16 genes were confirmed by qPCR. In addition, 14 candidate miRNA:mRNA reciprocal interactions were predicted. Several of the highly regulated genes and pathways were predicted as targets of miRNAs. Conclusions: We have described global transcriptional reprogramming during the progression of PKD in the \(Pkd1^{-/-}\) model. We propose a model for the cascade of signaling events involved in cyst formation and growth. Our results suggest that several miRNAs may be involved in regulating signaling pathways in ADPKD. We further describe novel putative miRNA:mRNA signatures in ADPKD, which will provide additional insights into the pathogenesis of this common genetic disease in humans.