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1.
Hideaki Nishihara Fumitaka Shimizu Yasuteru Sano Yukio Takeshita Toshihiko Maeda Masaaki Abe Michiaki Koga Takashi Kanda 《PloS one》2015,10(3)
Objective
Effect of fingolimod in multiple sclerosis (MS) is thought to involve the prevention of lymphocyte egress from lymphoid tissues, thereby reducing autoaggressive lymphocyte infiltration into the central nervous system across blood-brain barrier (BBB). However, brain microvascular endothelial cells (BMECs) represent a possible additional target for fingolimod in MS patients by directly repairing the function of BBB, as S1P receptors are also expressed by BMECs. In this study, we evaluated the effects of fingolimod on BMECs and clarified whether fingolimod-phosphate restores the BBB function after exposure to MS sera.Methods
Changes in tight junction proteins, adhesion molecules and transendothelial electrical resistance (TEER) in BMECs were evaluated following incubation in conditioned medium with or without fingolimod/fingolimod-phosphate. In addition, the effects of sera derived from MS patients, including those in the relapse phase of relapse-remitting (RR) MS, stable phase of RRMS and secondary progressive MS (SPMS), on the function of BBB in the presence of fingolimod-phosphate were assessed.Results
Incubation with fingolimod-phosphate increased the claudin-5 protein levels and TEER values in BMECs, although it did not change the amount of occludin, ICAM-1 or MelCAM proteins. Pretreatment with fingolimod-phosphate restored the changes in the claudin-5 and VCAM-1 protein/mRNA levels and TEER values in BMECs after exposure to MS sera.Conclusions
Pretreatment with fingolimod-phosphate prevents BBB disruption caused by both RRMS and SPMS sera via the upregulation of claudin-5 and downregulation of VCAM-1 in BMECs, suggesting that fingolimod-phosphate is capable of directly modifying the BBB. BMECs represent a possible therapeutic target for fingolimod in MS patients. 相似文献2.
The destruction of blood–brain barrier (BBB) and blood-nerve barrier (BNB) has been considered to be a key step in the disease
process of a number of neurological disorders including cerebral ischemia, Alzheimer’s disease, multiple sclerosis, and diabetic
neuropathy. Although glial cell line-derived neurotrophic factor (GDNF) and brain-derived neurotrophic factor (BDNF) facilitate
neuronal or axonal regeneration in the brain or peripheral nerves, their action in the BBB and BNB remains unclear. The purpose
of the present study was to elucidate whether these neurotrophic factors secreted from the brain or peripheral nerve pericytes
increase the barrier function of the BBB or BNB, using our newly established human brain microvascular endothelial cell (BMEC)
line or peripheral nerve microvascular endothelial cell (PnMEC) line. GDNF increased the expression of claudin-5 and the transendothelial
electrical resistance (TEER) of BMECs and PnMECs, whereas BDNF did not have this effect. Furthermore, we herein demonstrate
that the GDNF secreted from the brain and peripheral nerve pericytes was one of the key molecules responsible for the up-regulation
of claudin-5 expression and the TEER value in the BBB and BNB. These results indicate that the regulation of GDNF secreted
from pericytes may therefore be a novel therapeutic strategy to modify the BBB or BNB functions and promote brain or peripheral
nerve regeneration. 相似文献
3.
Dru S. Dace Aslam A. Khan Jennifer L. Stark Jennifer Kelly Anne H. Cross Rajendra S. Apte 《PloS one》2009,4(9)
Background
Demyelinating polyneuropathy is a debilitating, poorly understood disease that can exist in acute (Guillain-Barré syndrome) or chronic forms. Interleukin-10 (IL-10), although traditionally considered an anti-inflammatory cytokine, has also been implicated in promoting abnormal angiogenesis in the eye and in the pathobiology of autoimmune diseases such as lupus and encephalomyelitis.Principal Findings
Overexpression of IL-10 in a transgenic mouse model leads to macrophage-mediated demyelinating polyneuropathy. IL-10 upregulates ICAM-1 within neural tissues, promoting massive macrophage influx, inflammation-induced demyelination, and subsequent loss of neural tissue resulting in muscle weakness and paralysis. The primary insult is to perineural myelin followed by secondary axonal loss. Infiltrating macrophages within the peripheral nerves demonstrate a highly pro-inflammatory signature. Macrophages are central players in the pathophysiology, as in vivo depletion of macrophages using clodronate liposomes reverses the phenotype, including progressive nerve loss and paralysis. Macrophage-mediate demyelination is dependent on Fas-ligand (FasL)-mediated Schwann cell death.Significance
These findings mimic the human disease chronic idiopathic demyelinating polyneuropathy (CIDP) and may also promote further understanding of the pathobiology of related conditions such as acute idiopathic demyelinating polyneuropathy (AIDP) or Guillain-Barré syndrome. 相似文献4.
Steno Rinalduzzi Marco Serafini Marco Capozza Neri Accornero Paolo Missori Carlo Trompetto Francesco Fattapposta Antonio Currà 《PloS one》2016,11(3)
Introduction
Polyneuropathy leads to postural instability and an increased risk of falling. We investigated how impaired motor impairment and proprioceptive input due to neuropathy influences postural strategies.Methods
Platformless bisegmental posturography data were recorded in healthy subjects and patients with chronic inflammatory demyelinating polyradiculoneuropathy (CIDP). Each subject stood on the floor, wore a head and a hip electromagnetic tracker. Sway amplitude and velocity were recorded and the mean direction difference (MDD) in the velocity vector between trackers was calculated as a flexibility index.Results
Head and hip postural sway increased more in patients with CIDP than in healthy controls. MDD values reflecting hip strategies also increased more in patients than in controls. In the eyes closed condition MDD values in healthy subjects decreased but in patients remained unchanged.Discussion
Sensori-motor impairment changes the balance between postural strategies that patients adopt to maintain upright quiet stance. Motor impairment leads to hip postural strategy overweight (eyes open), and prevents strategy re-balancing when the sensory context predominantly relies on proprioceptive input (eyes closed). 相似文献5.
Background
Multiple sclerosis (MS) is less common in Asia, including Taiwan, and some characteristics of MS in Asians differ from those of Caucasians. Tumefactive brain lesion is even rarer in MS patients.Objective
To review patients with tumefactive MS and compare them with those in other studies investigating tumefactive demyelinating lesions and our Taiwanese typical MS patients.Methods
Twelve patients (6.3%) from the 190 MS patients visiting Taipei Veterans General Hospital from 1985 to 2010 were enrolled. They all fulfilled the McDonald or Poser criteria for MS and had at least one brain lesion larger than 2 centimeters with or without a mass effect.Results
Eleven patients (91.7%) were female and presented tumefactive brain lesions during the first attack. The clinical course of all patients was relapsing-remitting with a second attack within 2 years. Their initial extended disability status score was higher, but the prognosis was better after more than 2 years of follow-up, than in other studies. Moreover, our patients did not have optic or spinal involvement as well as positive neuromyelitis optica immunoglobulin or aquaporin-4 antibody, which is very common in Taiwanese MS patients.Conclusion
Tumefactive MS is not common in Taiwan. Although the tumefactive demyelinating lesions seem to be terrible initially, their prognosis is relatively more favorable than expected. 相似文献6.
Alon Abraham Hana Albulaihe Majed Alabdali Mohammad Qrimli Ari Breiner Carolina Barnett Hans D. Katzberg Leif E. Lovblom Bruce A. Perkins Vera Bril 《PloS one》2015,10(11)
Introduction
Vibration perception threshold (VPT) examination using a neurothesiometer provides objective, sensitive and specific information, and has been utilized mainly in patients with diabetic polyneropathy.Objectives
Explore the utility of VPT examination in CIDP patients.Methods
CIDP subjects attending the Neuromuscular clinic between 01/2013 and 12/2014 were evaluated. Demographic data, clinical history, physical examination, VPT values, and electrophysiologic data from their charts were extracted.Results
70 charts were reviewed. 55 CIDP patients had elevated VPT, associated with higher frequency of abnormal sensory testing for various modalities (92.7% vs. 46.7%, p<0.0001), lower sensory and motor amplitudes and reduced conduction velocities on nerve conduction studies, and lower treatment response rates (54% vs. 93%, p = 0.01).Conclusion
VPT examination is a simple tool, which is a reliable and sensitive measure not only for diabetic neuropathy, but also for CIDP. Moreover, in CIDP, elevated VPT values are also associated with lower treatment response rates. 相似文献7.
D Corridoni L Pastorelli B Mattioli S Locovei D Ishikawa KO Arseneau M Chieppa F Cominelli TT Pizarro 《PloS one》2012,7(7):e42067
Background
We previously showed that the probiotic mixture, VSL#3, prevents the onset of ileitis in SAMP/YitFc (SAMP) mice, and this effect was associated with stimulation of epithelial-derived TNF. The aim of this study was to determine the mechanism(s) of VSL#3-mediated protection on epithelial barrier function and to further investigate the “paradoxical” effects of TNF in preventing SAMP ileitis.Methods
Permeability was evaluated in SAMP mice prior to the onset of inflammation and during established disease by measuring transepithelial electrical resistance (TEER) on ex vivo-cultured ilea following exposure to VSL#3 conditioned media (CM), TNF or VSL#3-CM + anti-TNF. Tight junction (TJ) proteins were assessed by qRT-PCR, Western blot, and confocal microscopy, and TNFRI/TNFRII expression measured in freshly isolated intestinal epithelial cells (IEC) from SAMP and control AKR mice.Results
Culture with either VSL#3-CM or TNF resulted in decreased ileal paracellular permeability in pre-inflamed SAMP, but not SAMP with established disease, while addition of anti-TNF abrogated these effects. Modulation of the TJ proteins, claudin-2 and occludin, occurred with a significant decrease in claudin-2 and increase in occludin following stimulation with VSL#3-CM or TNF. TNF protein levels increased in supernatants of SAMP ilea incubated with VSL#3-CM compared to vehicle, while IEC-derived TNFR mRNA expression decreased in young, and was elevated in inflamed, SAMP versus AKR mice.Conclusions
Our data demonstrate that the previously established efficacy of VSL#3 in preventing SAMP ileitis is due to direct innate and homeostatic effects of TNF on the gut epithelium, modulation of the TJ proteins, claudin-2 and occludin, and overall improvement of intestinal permeability. 相似文献8.
Abe M Sano Y Maeda T Shimizu F Kashiwamura Y Haruki H Saito K Tasaki A Kawai M Terasaki T Kanda T 《Cell structure and function》2012,37(2):89-100
The blood-nerve barrier (BNB) is a highly specialized unit that maintains the microenvironments of the peripheral nervous system. Since the breakdown of the BNB has been considered a key step in autoimmune neuropathies such as Guillain-Barré syndrome and chronic inflammatory demyelinating polyraduculoneuropathy, it is important to understand the cellular properties of the peripheral nerve microvascular endothelial cells (PnMECs) which constitute the BNB. For this purpose, we established an immortalized cell line derived from human PnMECs. The human PnMECs were transduced with retroviral vectors encoding the temperature-sensitive SV40 large T antigen and human telomerase. This cell line, termed FH-BNB, showed a spindle fiber-shaped morphology, expression of von Willebrand factor and uptake of acetylated low density lipoprotein. These cells expressed tight junction proteins including occludin, claudin-5, ZO-1 and ZO-2 at the cell-cell boundaries. P-glycoprotein and GLUT-1 were also detected by a Western blot analysis and the cells exhibited the functional expression of p-glycoprotein. In addition, transendothelial electrical resistance experiments and paracellular permeabilities of sodium fluorescein and fluorescein isothiocyanate-labeled dextran of molecular weight 4 kDa across these cells demonstrated that FH-BNBs had functional tight junctions. These results indicated that FH-BNBs had highly specialized barrier properties and they might therefore be a useful tool to analyze the pathophysiology of various neuropathies. 相似文献
9.
10.
Dana Horakova Robert Zivadinov Bianca Weinstock-Guttman Eva Havrdova Jun Qu Miriam Tama?o-Blanco Darlene Badgett Michaela Tyblova Niels Bergsland Sara Hussein Laura Willis Jan Krasensky Manuela Vaneckova Zdenek Seidl Petra Lelkova Michael G. Dwyer Ming Zhang Haoying Yu Xiaotao Duan Tomas Kalincik Murali Ramanathan 《PloS one》2013,8(1)
Objectives
To investigate the associations of environmental MS risk factors with clinical and MRI measures of progression in high-risk clinically isolated syndromes (CIS) after the first demyelinating event.Methods
We analyzed 211 CIS patients (age: 28.9±7.8 years) enrolled in the SET study, a multi-center study of high-risk CIS patients. Pre-treatment samples were analyzed for IgG antibodies against cytomegalovirus (anti-CMV), Epstein Barr virus (EBV) early nuclear antigen-1 (EBNA-1), viral capsid antigen (VCA), early antigen-diffuse (EA-D), 25 hydroxy-vitamin D3 and cotinine levels and HLA DRB1*1501 status. The inclusion criteria required evaluation within 4 months of the initial demyelinating event, 2 or more brain MRI lesions and the presence of two or more oligoclonal bands in cerebrospinal fluid. All patients were treated with interferon-beta. Clinical and MRI assessments were obtained at baseline, 6, 12, and 24 months.Results
The time to first relapse decreased and the number of relapses increased with anti-CMV IgG positivity. Smoking was associated with increased number and volume of contrast-enhancing lesions (CEL) during the 2-year period. The cumulative number of CEL and T2 lesions during the 2-year period was greater for individuals in the highest quartile of anti-EBV VCA IgG antibodies. The percent loss of brain volume was increased for those in the highest quartile of with anti-EBV VCA IgG antibodies.Conclusions
Relapses in CIS patients were associated with CMV positivity whereas anti-EBV VCA positivity was associated with progression on MRI measures, including accumulation of CEL and T2 lesions and development of brain atrophy. 相似文献11.
Objective
Increasing evidences have suggested the pathogenic role of anti-neutrophil cytoplasmic antibodies (ANCA) directing myeloperoxidase (MPO) in ANCA-associated vasculitis (AAV). The current study aimed to analyze the association between the linear epitopes of MPO-ANCA and clinicopathological features of patients with AAV.Methods
Six recombinant linear fragments, covering the whole length amino acid sequence of a single chain of MPO, were produced from E.coli. Sera from 77 patients with AAV were collected at presentation. 13 out of the 77 patients had co-existence of serum anti-GBM antibodies. Ten patients also had sequential sera during follow up. The epitope specificities were detected by enzyme-linked immunosorbent assay using the recombinant fragments as solid phase ligands.Results
Sera from 45 of the 77 (58.4%) patients with AAV showed a positive reaction to one or more linear fragments of the MPO chain. The Birmingham Vasculitis Activity Scores and the sera creatinine were significantly higher in patients with positive binding to the light chain fragment than that in patients without the binding. The epitopes recognized by MPO-ANCA from patients with co-existence of serum anti-GBM antibodies were mainly located in the N-terminus of the heavy chain. In 5 out of the 6 patients, whose sera in relapse recognize linear fragments, the reactivity to linear fragments in relapse was similar to that of initial onset.Conclusion
The epitope specificities of MPO-ANCA were associated with disease activity and some clinicopathological features in patients with ANCA-associated vasculitis. 相似文献12.
Sano Y Shimizu F Nakayama H Abe M Maeda T Ohtsuki S Terasaki T Obinata M Ueda M Takahashi R Kanda T 《Cell structure and function》2007,32(2):139-147
In autoimmune disorders of the peripheral nervous system (PNS) such as Guillain-Barré syndrome and chronic inflammatory demyelinating polyradiculoneuropathy, breakdown of the blood-nerve barrier (BNB) has been considered as a key step in the disease process. Hence, it is important to know the cellular property of peripheral nerve microvascular endothelial cells (PnMECs) constituting the bulk of BNB. Although many in vitro models of the blood-brain barrier (BBB) have been established, very few in vitro BNB models have been reported so far. We isolated PnMECs from transgenic rats harboring the temperature-sensitive SV40 large T-antigen gene (tsA58 rat) and investigated the properties of these "barrier-forming cells". Isolated PnMECs (TR-BNBs) showed high transendothelial electrical resistance and expressed tight junction components and various types of influx as well as efflux transporters that have been reported to function at BBB. Furthermore, we confirmed the in vivo expression of various BBB-forming endothelial cell markers in the endoneurium of a rat sciatic nerve. These results suggest that PnMECs constituting the bulk of BNB have a highly specialized characteristic resembling the endothelial cells forming BBB. 相似文献
13.
Background and Purpose
Complications due to brain edema and breakdown of blood brain barrier are an important factor affecting the treatment effects of patients with severe carotid stenosis. In this study, we investigated the protective effects of ischemic postconditioning on brain edema and disruption of blood brain barrier via establishing rat model of hypoperfusion due to severe carotid stenosis.Methods
Wistar rat model of hypoperfusion due to severe carotid stenosis was established by binding a stainless microtube to both carotid arteries. Ischemic postconditioning procedure consisted of three cycles of 30 seconds ischemia and 30 seconds reperfusion. Brain edema was evaluated by measuring cerebral water content, and blood brain barrier permeability was assayed by examining cerebral concentration of Evans'' Blue (EB) and fluorescein sodium (NaF). ELISA was used to analyze the expression of MMP-9, claudin-5 and occludin. The activity and location of MMP-9 was analyzed by gelatin zymography and in situ zymography, respectively. The distribution of tight junction proteins claudin-5 and occludin was observed by immunohistochemistry.Results
The increased brain water content and cerebral concentration of EB and NaF were suppressed by administration of ischemic postconditioning prior to relief of carotid stenosis. Zymographic studies showed that MMP-9 was mainly located in the cortex and its activity was significantly improved by relief of carotid stenosis and, but the elevated MMP-9 activity was inhibited markedly by ischemic postconditioning. Immunohistochemistry revealed that ischemic postconditioning improved the discontinuous distribution of claudin-5 and occludin. ELISA detected that the expression of up-regulated MMP-9 and down-regulated claudin-5 and occludin caused by carotid relief were all attenuated by ischemic postconditioning.Conclusions
Ischemic postconditioning is an effective method to prevent brain edema and improve BBB permeability and could be used during relief of severe carotid stenosis. 相似文献14.
Caroline Charpin Fanny Arnoux Marielle Martin Eric Toussirot Nathalie Lambert Nathalie Balandraud Daniel Wendling Elisabeth Diot Jean Roudier Isabelle Auger 《Arthritis research & therapy》2013,15(4):R78
Introduction
Rheumatoid arthritis (RA) is a chronic inflammatory joint disease causing articular cartilage and bone destruction. Since irreversible joint destruction can be prevented by intervention at the early stages of disease, early diagnosis of RA is important. In this study, we identified new autoantibodies in the sera of patients with early (less than one year) RA.Methods
We screened the sera of 20 RA patients with disease duration less than one year, 19 RA patients with disease duration more than five years and 23 controls on 8,268 human protein arrays. We confirmed the validity of protein array detection by ELISA assays. We then performed epitope mapping with overlapping 15-mers to analyze RA sera reactivity.Results
WIBG (within BGCN homolog (Drosophila)), GABARAPL2 (GABA(A) receptor associated protein like 2) and ZNF706 (zinc finger protein 706) proteins are preferentially recognized by autoantibodies from early RA patients. Of interest, autoantibodies to WIBG are very specific for early RA. Indeed, 33% of early RA patients'' sera recognize WIBG versus 5% of RA patients with disease duration more than 5 years and 2% of controls. We identified three linear peptides on WIBG GABARAPL2 and ZNF706 that are preferentially recognized by sera of early RA patients.Conclusions
We identified new autoantibodies associated with RA with disease duration less than one year. These autoantibodies could be used as diagnosis markers in RA patients. 相似文献15.
16.
Joyce JBC van Beers Annemiek Willemze Jeroen J Jansen Gerard HM Engbers Martin Salden Jos Raats Jan W Drijfhout Annette HM van der Helm-van Mil Rene EM Toes Ger JM Pruijn 《Arthritis research & therapy》2013,15(5):R140
Introduction
Autoantibodies against citrullinated peptides/proteins (ACPA) are found in approximately 75% of the sera of patients with rheumatoid arthritis (RA). The RA-specific ACPA are frequently present prior to disease onset and their presence associates with a more erosive disease course. ACPA can therefore be used to aid the diagnosis and prognosis of RA. Recently, it became clear that ACPA are very heterogeneous, both in an individual patient and among different patients. The aim of this study was to investigate whether clinically meaningful ACPA profiles exist in early RA patients.Methods
Twenty citrullinated peptides and the corresponding non-citrullinated control peptides were immobilized on microarray sensor chips. Sera from 374 early arthritis patients were analyzed by surface plasmon resonance imaging (iSPR) of biomolecular interactions on the sensor chip.Results
Cluster analysis of the reactivities with the citrullinated peptides, after subtraction of the reactivities with the corresponding control peptides confirmed the heterogeneity of the ACPA response in RA and revealed 12 distinct ACPA profiles. The association of the 5 most frequent profiles with clinical features at diagnosis and during the disease course was examined, showing no statistically significant associations.Conclusions
Compared to the detection of ACPA in RA sera by CCP-based assays, ACPA profiling in early arthritis patients did not reveal associations with disease activity and progression scores. 相似文献17.
Philipp B?umer Markus Weiler Maurice Ruetters Frank Staub Thomas Dombert Sabine Heiland Martin Bendszus Mirko Pham 《PloS one》2012,7(11)
Purpose
Patients with ulnar neuropathy of unclear etiology occasionally present with lesion extension from elbow to upper arm level on MRI. This study investigated whether MRI thereby distinguishes multifocal neuropathy from focal-compressive neuropathy at the elbow.Methods
This prospective study was approved by the institutional ethics committee and written informed consent was obtained from all participants. 122 patients with ulnar mononeuropathy of undetermined localization and etiology by clinical and electrophysiological examination were assessed by MRI at upper arm and elbow level using T2-weighted fat-saturated sequences at 3T. Twenty-one patients were identified with proximal ulnar nerve lesions and evaluated for findings suggestive of disseminated neuropathy (i) subclinical lesions in other nerves, (ii) unfavorable outcome after previous decompressive elbow surgery, and (iii) subsequent diagnosis of inflammatory or other disseminated neuropathy. Two groups served as controls for quantitative analysis of nerve-to-muscle signal intensity ratios: 20 subjects with typical focal ulnar neuropathy at the elbow and 20 healthy subjects.Results
In the group of 21 patients with proximal ulnar nerve lesion extension, T2-w ulnar nerve signal was significantly (p<0.001) higher at upper arm level than in both control groups. A cut-off value of 1.92 for maximum nerve-to-muscle signal intensity ratio was found to be sensitive (86%) and specific (100%) to discriminate this group. Ten patients (48%) exhibited additional T2-w lesions in the median and/or radial nerve. Another ten (48%) had previously undergone elbow surgery without satisfying outcome. Clinical follow-up was available in 15 (71%) and revealed definitive diagnoses of multifocal neuropathy of various etiologies in four patients. In another eight, diagnoses could not yet be considered definitive but were consistent with multifocal neuropathy.Conclusion
Proximal ulnar nerve T2 lesions at upper arm level are detected by MRI and indicate the presence of a non-focal disseminated neuropathy instead of a focal compressive neuropathy. 相似文献18.
Anne Becker Nicole Ludwig Andreas Keller Bj?rn Tackenberg Christian Eienbr?ker Wolfgang H. Oertel Klaus Fassbender Eckart Meese Klemens Ruprecht 《PloS one》2013,8(3)
Background
Myasthenia gravis is a disorder of neuromuscular transmission associated with autoantibodies against the nicotinic acetylcholine receptor. We have previously developed a customized protein macroarray comprising 1827 potential human autoantigens, which permitted to discriminate sera of patients with different cancers from sera of healthy controls, but has not yet been evaluated in antibody-mediated autoimmune diseases.Objective
To determine whether autoantibody signatures obtained by protein macroarray separate sera of patients with myasthenia gravis from healthy controls.Methods
Sera of patients with acetylcholine receptor antibody-positive myasthenia gravis (n = 25) and healthy controls (n = 32) were analyzed by protein macroarrays comprising 1827 peptide clones.Results
Autoantibody signatures did not separate patients with myasthenia gravis from controls with sufficient sensitivity, specificity, and accuracy. Intensity values of one antigen (poly A binding protein cytoplasmic 1, p = 0.0045) were higher in patients with myasthenia gravis, but the relevance of this and two further antigens, 40S ribosomal protein S13 (20.8% vs. 0%, p = 0.011) and proteasome subunit alpha type 1 (25% vs. 3.1%, p = 0.035), which were detected more frequently by myasthenia gravis than by control sera, currently remains uncertain.Conclusion
Seroreactivity profiles of patients with myasthenia gravis detected by a customized protein macroarray did not allow discrimination from healthy controls, compatible with the notion that the autoantibody response in myasthenia gravis is highly focussed against the acetylcholine receptor. 相似文献19.
Riitta Kaarteenaho Heta Merikallio Siri Lehtonen Terttu Harju Ylermi Soini 《Respiratory research》2010,11(1):59
Background
Claudins are the main components of tight junctions, structures which are associated with cell polarity and permeability. The aim of this study was to analyze the expression of claudins 1, 3, 4, 5, and 7 in developing human lung tissues from 12 to 40 weeks of gestation.Methods
47 cases were analyzed by immunohistochemisty for claudins 1, 3, 4, 5 and 7. 23 cases were also investigated by quantitative RT-PCR for claudin-1, -3 and -4.Results
Claudin-1 was expressed in epithelium of bronchi and large bronchioles from week 12 onwards but it was not detected in epithelium of developing alveoli. Claudin-3, -4 and -7 were strongly expressed in bronchial epithelium from week 12 to week 40, and they were also expressed in alveoli from week 16 to week 40. Claudin-5 was expressed strongly during all periods in endothelial cells. It was expressed also in epithelium of bronchi from week 12 to week 40, and in alveoli during the canalicular period. RT-PCR analyses revealed detectable amounts of RNAs for claudins 1, 3 and 4 in all cases studied.Conclusion
Claudin-1, -3, -4, -5, and -7 are expressed in developing human lung from week 12 to week 40 with distinct locations and in divergent quantities. The expression of claudin-1 was restricted to the bronchial epithelium, whereas claudin-3, -4 and -7 were positive also in alveolar epithelium as well as in the bronchial epithelium. All claudins studied are linked to the development of airways, whereas claudin-3, -4, -5 and -7, but not claudin-1, are involved in the development of acinus and the differentiation of alveolar epithelial cells. 相似文献20.
Tilo W. Eichler Cecilie Totland Mette Haugen Tor H. Qvale Kibret Mazengia Anette Storstein Bj?rn I. Haukanes Christian A. Vedeler 《PloS one》2013,8(6)