Biomedical subjects

Y Jia

Publications and source records attributed to Y Jia.

At least 19 recordsLinked to original sources

PubMed2006

Sulfur-dioxide exposure increases TRPV1-mediated responses in nodose ganglia cells and augments cough in guinea pigs.

The objective of the present experiments was to study the effects of pulmonary inflammation induced by subacute Sulfur-dioxide (SO(2)) exposure on capsaicin-induced responses in isolated primary vagal sensory neurons and cough. Additionally, we examined the effects of SO(2) exposure on respiratory function and lung histology. All experiments were conducted 24 h after 4 days of subacute SO(2) (1000 ppm, 3 h/day for 4 days) exposure. In in vitro experiments, intracellular Ca(2+) concentrations were measured in single nodose ganglia cells isolated from SO(2) treated and control guinea pigs, using a fluorescence-based methodology. In nodose ganglia cells from SO(2)-exposed animals, intracellular Ca(2+) responses evoked by capsaicin (1 x 10(-7) and 1 x 10(-6) M) were significantly augmented (87% and 59%, respectively) compared to nodose ganglia from control animals. In vivo experiments, cough responses induced by a submaximal dose of aerosolized capsaicin (30 microM) were increased approximately 50% in SO(2) exposed animals compared to control animals. The enhanced cough response produced by SO(2) was inhibited by the corticosteroid, dexamethasone (10 mg/kg, p.o. b.i.d for 4 days and 10 mg/kg, p.o. once on day 5). In separate experiments, guinea pigs exposed to SO(2) displayed a decrease in respiratory frequency and minute ventilation and an increase in enhanced pause (PenH), a surrogate measure for pulmonary obstruction. Associated with the SO(2)-induced increase in cough and changes in respiratory parameters was an increase in BAL neutrophils. BAL neutrophil counts were 5+/-4 and 691+/-141 cells x 10(3)/ml for air and SO(2)-exposed animals, respectively. The neutrophillic inflammation induced by SO(2) was attenuated by dexamethasone treatment. Finally, staining for collagen, smooth muscle and goblet cells showed inflammation, remodeling and goblet cell metaphasia in the SO(2)-exposed animals. Our results demonstrate that SO(2) exposure enhances TRPV1 receptor function at the level of the nodose ganglia. This effect occurs in parallel with an increase sensitivity of the cough response to capsaicin.

Air Pollutants↗

PubMed2006

Different effects of insulin and insulin-like growth factors I and II on osteoprogenitors and adipocyte progenitors in fetal rat bone cell populations.

We investigated the effects of insulin (1-1,000 nM), insulin-like growth factor (IGF)-I, and IGF-II (3-100 nM each) alone or together with 10 nM dexamethasone (DEX) or 10 nM 1,25-dihydroxyvitamin D(3) (1,25[OH](2)D(3)) on proliferation and differentiation of adipocyte and osteoblast progenitors in bone cell populations derived from fetal rat calvaria. The effects on differentiation were evaluated by counting the number of bone or osteoid nodules and adipocyte colonies and the effects on proliferation, by measuring their size by image analysis. The types of cells studied were 1,25(OH)(2)D(3)- and DEX-responsive adipocyte progenitors and DEX-dependent and independent osteoprogenitors. Both IGF-I and IGF-II stimulated osteoprogenitor differentiation both alone and in the presence of DEX, while insulin stimulated osteoprogenitor differentiation only in the absence of DEX. Neither IGF-I/-II nor insulin affected proliferation of osteoprogenitors. Insulin had little effect on adipocyte differentiation by itself but strongly stimulated differentiation in the presence of either 1,25(OH)(2)D(3) or DEX, while IGF-II stimulated adipocyte differentiation in both the absence and presence of 1,25(OH)(2)D(3) or DEX. IGF-I by itself or in the presence of DEX strongly stimulated adipocyte cell differentiation but had little effect in the presence of 1,25(OH)(2)D(3). Our results demonstrate that insulin, IGF-II, and IGF-I have specific and different effects on the differentiation and proliferation of different groups of progenitor cells.

Adipocytes↗

PubMed2006

Single-walled carbon nanotubes-mediated in vivo and in vitro delivery of siRNA into antigen-presenting cells.

Antigen-presenting cells such as dendritic cells (DCs) play a critical role in inducing and regulating immune responses. One effective strategy for DC-based immunotherapy is to regulate maturation and function of DC. In this study, we apply single-walled carbon nanotubes (SWNTs) to carry small interfering RNA (siRNA) to reach, enter and genetically modify DCs in vivo. We prepared positively charged SWNTs (SWNTs+) using 1,6-diaminohexane which was demonstrated by transmission electron microscopy equipped with energy-dispersive X-ray spectroscopy and atomic force microscope. The functionalized SWNTs+ could absorb siRNA to form complexes of siRNA with SWNTs. These siRNA:SWNT+ complexes were preferentially taken up by splenic CD11c+ DCs, CD11b+ cells and also Gr-1+CD11b+ cells comprising DCs, macrophages and other myeloid cells to silence the targeting gene. Suppressor of cytokine signaling 1 (SOCS1) restricts the ability of DCs to break self-tolerance and induce antitumor immunity. Infusion of SWNTs+ carrying SOCS1siRNA reduced SOCS1 expression and retarded the growth of established B16 tumor in mice, indicating the possibility of in vivo immunotherapeutics using SWNTs-based siRNA transfer system.

Animals↗

PubMed2006

Prevention of murine experimental autoimmune encephalomyelitis by in vivo expression of a novel recombinant immunotoxin DT390-RANTES.

Experimental autoimmune encephalomyelitis (EAE) is a T-cell-mediated autoimmune disease. Chemokine receptor CCR5 has been shown to be essential for the T-cell recruitment to the inflammatory site in EAE. In this study, we assumed that an immunotoxin directed at CCR5+ cells would be able to reduce the disease activity of EAE. A recombinant immunotoxin, DT390-RANTES-SRalpha, was constructed in an eukaryotic cell expression plasmid consisting of regulated on activation normal T cells expressed and secreted (RANTES) as the targeting moiety and DT390 as the toxic moiety. DT390-RANTES was expressed in vitro and was highly toxic to activated mouse T cells with the inhibitory concentration 50 at 0.18 ng/ml. To evaluate whether DT390-RANTES was effective in preventing EAE, C57BL/6 mice were immunized with myelin basic protein, emulsified with complete Freund's adjuvant and were treated by injecting cationic liposome-embedded plasmid DNA into the muscle of hind limbs. Mice treated with DT390-RANTES-SRalpha developed a much milder EAE compared to mice treated with phosphate-buffered saline or the empty plasmid DNA. Much less CCR5+-infiltrating cells were found in the central nervous system in DT390-RANTES-SRalpha-treated mice than in the control mice. This study indicates that recombinant immunotoxin can be expressed in vivo, and targeting CCR5 can attenuate the disease activity of EAE in mice.

3T3 Cells↗

PubMed2006

alpha2-adrenoceptor agonists as nasal decongestants.

Nasal congestion, one of the major disease features of rhinitis, is induced by the filling of venous sinusoids causing mucosal engorgement with resultant obstruction of nasal airflow. The only available drugs that directly target the underlying vascular features driving nasal obstruction are the sympathomimetic alpha-adrenoceptor agonists due to their vasoconstrictor action. However, standard decongestants are nonselective alpha-adrenoceptor agonists, which have the potential for side-effects liabilities such as hypertension, stroke, insomnia and nervousness. In the present study, the effects of nonsubtype selective alpha(2)-adrenoceptor agonists BHT-920 and PGE-6201204 were evaluated in several isolated nasal mucosa contractile bioassays including dog, pig and monkey, and in a real-time tissue contractility assay using isolated pig nasal explants for BHT-920. The decongestant activity of PGE-6201204 was evaluated in vivo in a cat model of experimental congestion. Our results showed that alpha(2)-adrenoceptor agonists (1) contract nasal mucosa of different species, (2) exert a preferential vasoconstrictor effect on the capacitance vessels (veins and sinusoids), and (3) elicit decongestion. In conclusion, a selective alpha(2)-adrenoceptor agonist causing constriction preferentially in the large venous sinusoids and veins of nasal mucosa and producing nasal decongestion is expected to show efficacy in the treatment of nasal congestion without the characteristic arterio-constrictor action of the standard nonselective sympathomimetic decongestants.

Adrenergic alpha-2 Receptor Agonists↗

PubMed2005

Electric field-induced magnetization switching in epitaxial columnar nanostructures.

We present direct evidence for room-temperature magnetization reversal induced by an electric field in epitaxial ferroelectric BiFeO3-ferrimagnetic CoFe2O4 columnar nanostructures. Piezoelectric force microscopy and magnetic force microscopy were used to locally image the coupled piezoelectric-magnetic switching. Quantitative analyses give a perpendicular magnetoelectric susceptibility of approximately 1.0 x 10(-2) G cm/V. The observed effect is due to the strong elastic coupling between the two ferric constituents as the result of the three-dimensional heteroepitaxy.

Journal Article↗

PubMed2004

Self-assembled single-crystal ferromagnetic iron nanowires formed by decomposition.

Arrays of perpendicular ferromagnetic nanowires have recently attracted considerable interest for their potential use in many areas of advanced nanotechnology. We report a simple approach to create self-assembled nanowires of alpha-Fe through the decomposition of a suitably chosen perovskite. We illustrate the principle behind this approach using the reaction 2La(0.5)Sr(0.5)FeO(3) --> LaSrFeO(4) + Fe + O(2) that occurs during the deposition of La(0.5)Sr(0.5)FeO(3) under reducing conditions. This leads to the spontaneous formation of an array of single-crystalline alpha-Fe nanowires embedded in LaSrFeO(4) matrix, which grow perpendicular to the substrate and span the entire film thickness. The diameter and spacing of the nanowires are controlled directly by deposition temperature. The nanowires show uniaxial anisotropy normal to the film plane and magnetization close to that of bulk alpha-Fe. The high magnetization and sizable coercivity of the nanowires make them desirable for high-density data storage and other magnetic-device applications.

Crystallization↗

PubMed2004

Cloning and sequence analysis of a low temperature-induced gene from trifoliate orange with unusual pre-mRNA processing.

Exposure of cold-hardy Rubidoux trifoliate orange [Poncirus trifoliata (L) Raf.] plants to temperatures from 28 degrees C to -5 degrees C enabled us to isolate and characterize a novel citrus low-temperature gene (CLT) with two transcripts, called CLTa and CLTb, from leaves and stems. CLTa was produced when plants were subjected to low temperatures (starting at 10 degrees C), while CLTb was constitutively expressed. Both CLTa and CLTb have the same open reading frame (ORF) of 165 nucleotides and encode a small (54 deduced amino acid) protein. However, CLTa has an additional 98 nucleotides in the 3'-untranslated region (UTR) that are absent in CLTb. Expression analysis using relative quantitative RT-PCR demonstrated that CLTa is expressed exclusively at low temperatures, while CLTb is expressed constitutively (expression verified from 33 degrees C to -5 degrees C). A GenBank database search identified 61 nucleotides inside of the ORF that are highly similar to low-temperature-responsive genes from Arabidopsis thaliana and Solanum tuberosum. The deduced amino acid sequence revealed similarity with low-temperature-responsive proteins from A. thaliana, Oryza sativa, and S. tuberosum of 77%, 81%, and 73.9%, respectively. A genomic clone was isolated, and the genome organization revealed the presence of three exons and two introns, the second of which is in the 3' UTR and participates in alternative 3' splice site selection. One of the 3' splice sites of the second intron was located immediately before the additional 98-bp non-coding fragment of CLTa, and the second at the very end of the 98-bp fragment. Additionally, the presence of the tetranucleotides TCTT and TTCT, which are involved in the regulation of transcript processing in animals and possibly also active in peach, was found in this intron. Competition for splicing sites on the pre-mRNA in the spliceosome, which is induced by low temperature, may be involved in the production of the two transcripts of the CLT gene.

Acclimatization↗

PubMed2004

Multiferroic BaTiO3-CoFe2O4 Nanostructures.

We report on the coupling between ferroelectric and magnetic order parameters in a nanostructured BaTiO3-CoFe2O4 ferroelectromagnet. This facilitates the interconversion of energies stored in electric and magnetic fields and plays an important role in many devices, including transducers, field sensors, etc. Such nanostructures were deposited on single-crystal SrTiO3 (001) substrates by pulsed laser deposition from a single Ba-Ti-Co-Fe-oxide target. The films are epitaxial in-plane as well as out-of-plane with self-assembled hexagonal arrays of CoFe2O4 nanopillars embedded in a BaTiO3 matrix. The CoFe2O4 nanopillars have uniform size and average spacing of 20 to 30 nanometers. Temperature-dependent magnetic measurements illustrate the coupling between the two order parameters, which is manifested as a change in magnetization at the ferroelectric Curie temperature. Thermodynamic analyses show that the magnetoelectric coupling in such a nanostructure can be understood on the basis of the strong elastic interactions between the two phases.

Journal Article↗

PubMed2003

Proliferation, differentiation and self-renewal of osteoprogenitors in vertebral cell populations from aged and young female rats.

A significant contribution to the bone loss associated with aging is likely to be a decline in bone formation. We have characterized and compared the number, capacity for proliferation and differentiation and the self-renewal ability of osteoprogenitors of aged (17-26-month-old) and young (1.5-month-old) female Wistar rats using limiting dilution analyses and continuous subculture experiments. Cells were obtained from outgrowths of explants of lumbar vertebrae (L1-L6) and grown in alpha-minimal essential medium (alpha-MEM), 10% FBS and 50 microg/ml ascorbic acid with or without dexamethasone (Dex; 0.3-300 nM) or progesterone (Prog; 0.01-10 microM). Growth curves for cell populations of both age groups were similar with population doubling times of 27.1 and 26.7 h for the aged and young animals, respectively. Osteoprogenitors from both age groups formed bone nodules when cultured in the presence of either Dex or Prog. Limiting dilution analysis in the presence of 10 nM Dex showed no difference between the aged and young rats in the number of colony forming units-fibroblast (CFU-F), alkaline phosphatase-positive colony forming units-fibroblast (AP+ CFU-F) or colony forming units-osteoblast (CFU-O). No differences were also found for any progenitor within the aged group. Limiting dilution analysis in the presence of 3 microM Prog showed no differences in the numbers of CFU-F, AP+ CFU-F or CFU-O between the aged and young groups or within the aged group. Continuous subculture of cells in the presence of 10 nM Dex revealed that the number of nodules per 10(4) plated cells increased in second subculture over first subculture cells in the young group but decreased in the aged group. Also, in third to fifth subculture cells, the number of nodules was lower in the aged group than in the young group. A similar pattern was observed in the presence of 3 microM Prog. Results indicate that the cell population doubling times, growth characteristics, and the number of CFU-F and osteoprogenitors in vertebral bone cell populations from aged rats and young rats are similar. This suggests that the bone loss associated with aging is not caused by a decrease in osteoprogenitor cell number. However, cell populations from the aged rats showed a reduced capacity for self-renewal in vitro, which would ultimately translate into a reduced number of osteoblasts and might be partly responsible for a decrease in bone formation in aged animals.

Aging↗

PubMed2002

The neuronal migration defect in mice with Zellweger syndrome (Pex5 knockout) is not caused by the inactivity of peroxisomal beta-oxidation.

The purpose of this study was to investigate whether deficient peroxisomal beta-oxidation is causally involved in the neuronal migration defect observed in Pex5 knockout mice. These mice are models for Zellweger syndrome, a peroxisome biogenesis disorder. Neocortical development was evaluated in mice carrying a partial or complete defect of peroxisomal beta-oxidation at the level of the second enzyme of the pathway, namely, the hydratase-dehydrogenase multifunctional/bifunctional enzymes MFP1/L-PBE and MFP2/D-PBE. In contrast to patients with multifunctional protein 2 deficiency who present with neocortical dysgenesis, impairment of neuronal migration was not observed in the single MFP2 or in the double MFP1/MFP2 knockout mice. At birth, the double knockout pups displayed variable growth retardation and about one half of them were severely hypotonic, whereas the single MFP2 knockout animals were all normal in the perinatal period. These results indicate that in the mouse, defective peroxisomal beta-oxidation does not cause neuronal migration defects by itself. This does not exclude that the inactivity of this metabolic pathway contributes to the brain pathology in mice and patients with complete absence of functional peroxisomes.

Animals↗

PubMed2001

Increase in cytochrome oxidase activity in regenerating nerve fibers of hemitransected spinal cord in the rat.

We explored the possibility of cytochrome oxidase (CO) involvement in spinal cord regeneration in adult rats. The spinal cord was hemitransected at T9. After one month's survival, the animals were deeply anesthetized and perfused. The spinal cord segments including the lesion site were removed and sectioned horizontally for CO histochemistry. Under light microscope, a substantial number of CO-reactive nerve fibers and boutons were identified in the lateral funiculus adjacent to the lesion site. Under electron microscope, moderately to highly CO-reactive mitochondria could be seen within nerve fibers and boutons. Synaptic contacts were identified among them. The increase in CO activity in nerve fibers and boutons may indicate their high-energy demand for synaptic and spontaneous activity following spinal cord hemisection.

Animals↗

PubMed2001

Class I and III polyhydroxyalkanoate synthases from Ralstonia eutropha and Allochromatium vinosum: characterization and substrate specificity studies.

Class I and III polyhydroxyalkanoate (PHA) synthases catalyze the conversion of beta-hydroxybutyryl coenzyme A (HBCoA) to polyhydroxybutyrate. The Class I PHA synthase from Ralstonia eutropha has been purified by numerous labs with reported specific activities that vary between 1 and 160 U/mg. An N-terminal (His)6-PHA synthase was constructed and purified with specific activity of 40 U/mg. The variable activity is shown to be related to the protein's propensity to aggregate and not to incomplete post-translational modification by coenzyme A and a phosphopantetheinyl transferase. The substrate specificities of this enzyme and the Class III PHA synthase from Allochromatium vinosum have been determined with nine analogs of varied chain length and branching, OH group position within the chain, and thioesters. The results suggest that in vitro, both PHA synthases are very specific and provide further support for their active site structural similarities. In vitro results differ from studies in vivo.

Acyltransferases↗

PubMed2001

Human peroxisome proliferator-activated receptor alpha (PPARalpha) supports the induction of peroxisome proliferation in PPARalpha-deficient mouse liver.

Peroxisome proliferators, which function as peroxisome proliferator-activated receptor alpha (PPARalpha) agonists, induce peroxisomal, microsomal, and mitochondrial fatty acid oxidation enzymes, in conjunction with peroxisome proliferation, in liver cells. Sustained activation of PPARalpha leads to the development of liver tumors in rats and mice. The assertion that synthetic PPARalpha ligands pose negligible carcinogenic risk to humans is attributable, in part, to the failure to observe peroxisome proliferation in human hepatocytes. To explore the mechanism(s) of species-specific differences in response to PPARalpha ligands, we determined the functional competency of human PPARalpha in vivo and compared its potency with that of mouse PPARalpha. Recombinant adenovirus that expresses human or mouse PPARalpha was produced and administered intravenously to PPARalpha-deficient mice. Human as well as mouse PPARalpha fully restored the development of peroxisome proliferator-induced immediate pleiotropic responses, including peroxisome proliferation and enhanced expression of genes involved in lipid metabolism as well as nonperoxisomal genes, such as CD36, Ly-6D, Rbp7, monoglyceride lipase, pyruvate dehydrogenase kinase-4, and C3f, that have been identified recently to be up-regulated in livers with peroxisome proliferation. These studies establish that human PPARalpha is functionally competent and is equally as dose-sensitive as mouse PPARalpha in inducing peroxisome proliferation within the context of mouse liver environment and that it can heterodimerize with mouse retinoid X receptor, and this human PPARalpha-mouse retinoid X receptor chimeric heterodimer transcriptionally activates mouse PPARalpha target genes in a manner qualitatively similar to that of mouse PPARalpha.

Animals↗

PubMed2001

Identification and characterization of hic-5/ARA55 as an hsp27 binding protein.

hsp27 has been reported to participate in a wide variety of activities, including resistance to thermal and metabolic stress, regulation of growth and differentiation, and acting as a molecular chaperone or a regulator of actin polymerization. We hypothesized that these diverse functions are regulated in a cell- or tissue-specific manner via interaction with various binding proteins. To investigate this hypothesis, we used hsp27 as a "bait" to screen a yeast two-hybrid cDNA library from rat kidney glomeruli and identified a novel hsp27 binding protein, hic-5 (also known as ARA55), a focal adhesion protein and steroid receptor co-activator. Biochemical interaction between hsp27 and hic-5 was confirmed by co-immunoprecipitation, and critical protein.protein interaction regions were mapped to the hic-5 LIM domains and the hsp27 C-terminal domain. Initial analysis of the functional role of hsp27.hic-5 interaction revealed that hic-5 significantly inhibited the protection against heat-induced cell death conferred by hsp27 overexpression in co-transfected 293T cells. In contrast, when a non-hsp27-interacting hic-5 truncation mutant (hic-5/DeltaLIM4) was co-expressed with hsp27, the hic-5 inhibition of hsp27 protection was absent. We conclude that hic-5 is a true hsp27 binding protein and inhibits the ability of hsp27 to provide protection against heat shock in an interaction-dependent manner.

Amino Acid Sequence↗

PubMed2001

Peroxisome proliferator-activated receptor alpha-responsive genes induced in the newborn but not prenatal liver of peroxisomal fatty acyl-CoA oxidase null mice.

Mice deficient in fatty acyl-CoA oxidase (AOX(-/-)), the first enzyme of the peroxisomal beta-oxidation system, develop specific morphological and molecular changes in the liver characterized by microvesicular fatty change, increased mitosis, spontaneous peroxisome proliferation, increased mRNA and protein levels of genes regulated by peroxisome proliferator-activated receptor alpha (PPARalpha), and hepatocellular carcinoma. Based on these findings it is proposed that substrates for AOX function as ligands for PPARalpha. In this study we examined the sequential changes in morphology and gene expression in the liver of wild-type and AOX(-/-) mice at Embryonic Day 17.5, and during postnatal development up to 2 months of age. In AOX(-/-) mice high levels of expression of PPARalpha-responsive genes in the liver commenced on the day of birth and persisted throughout the postnatal period. We found no indication of PPARalpha activation in the livers of AOX(-/-) mice at embryonic age E17.5. In AOX(-/-) mice microvesicular fatty change in liver cells was evident at 7 days. At 2 months of age livers showed extensive steatosis and the presence in the periportal areas of clusters of hepatocytes with abundant granular eosinophilic cytoplasm rich in peroxisomes. These results suggest that the biological ligands for PPARalpha vis a vis substrates for AOX either are not functional in fetal liver or do not cross the placental barrier during the fetal development and that postnatally they are likely derived from milk and diet.

3-Hydroxyacyl CoA Dehydrogenases↗

PubMed2001

Effects of glutaraldehyde polymerization on oxygen transport and redox properties of bovine hemoglobin.

Crosslinking of bovine Hb (HbBv) with glutaraldehyde produces a mixture of low oxygen affinity (P(50)) tetrameric and polymeric Hb species (PolyHbBv). Under physiological conditions the P(50) of HbBv and PolyHbBv were 27 and 35 mmHg, respectively. The dependence of the P(50) on pH and chloride ions and the cooperativity (n(50)) of the protein were diminished as a result of glutaraldehyde modification. Rapid kinetic studies showed greater overall rates of oxygen dissociation (k(off)) with little or no change in the association of CO (k(on)) to the modified protein. The rate of nitric oxide (NO)-induced oxidation of the PolyHbBv was slightly lower than that of HbBv. Autoxidation rate of PolyHbBv was 1.4 times faster than that of HbBv. The reaction of hydrogen peroxide (H2O2) with the ferrous (Fe(2+)) and ferric (Fe(3+)) forms of the proteins led to the formation of a more stable ferrylHb (Fe(4+)) in the case of PolyHbBv. Glutaraldehyde polymerization of HbBv alters its normal allosteric mechanisms, autoxidation kinetics and other related redox properties, which may compromise its function and cause greater toxicity when used as an oxygen transport fluid.

Animals↗

PubMed2001

Regulation of the CFTR channel by phosphorylation.

Cystic fibrosis transmembrane conductance regulator (CFTR) chloride channels are regulated tightly by protein kinases and phosphatases. The regulatory domain of CFTR has about 20 potential sites for phosphorylation by protein kinases A (PKA) and C (PKC). The reason for this large number of sites is not known, however their conservation from fish to humans implies that they play important roles in vivo. PKA is an important activator, and its stimulation of CFTR is enhanced by PKC via mechanisms which are not fully understood. The physiological stimuli of CFTR are not known for some epithelia, and it appears likely that other serine/threonine and even tyrosine kinases also regulate CFTR in particular tissues. Phosphatases that deactivate CFTR have yet to be identified definitively at the molecular level, however CFTR is regulated by a membrane-bound form of protein phosphatase-2C (PP2C) in several cell types. Patch-clamp studies of channel rundown, co-immunoprecipitation, chemical cross-linking studies, and pull-down assays all indicate that CFTR and PP2C are closely associated within a stable regulatory complex. Understanding the regulation of CFTR by PP2C is a priority due to its potential as a target for pharmacotherapies in the treatment of cystic fibrosis.

Cystic Fibrosis↗