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1.
J Clin Med ; 12(16)2023 Aug 13.
Article in English | MEDLINE | ID: mdl-37629311

ABSTRACT

Recently, there has been increasing interest in medial meniscal extrusion (MME), but few reports have evaluated MME via X-ray. In this study, the amount of MME and meniscal height at the medial border of the tibia were measured via X-ray with gradation processing. The extrusion length divided by the meniscal height yields the meniscal extrusion ratio, which was used as an index. In addition, the medial meniscal length of the part protruding from the medial border of the tibia on MRI was measured as an absolute value. Then, the correlation between the meniscal extrusion ratio and the amount of MME on MRI was examined, and there was a strong correlation between the meniscal extrusion ratio via X-ray and the amount of MME on MRI (correlation coefficient 0.860, p < 0.0001). The cut-off value of the meniscal extrusion ratio via X-ray for positive meniscal extrusion on MRI was 0.50, with an AUC of 0.9825, sensitivity of 0.9063, and specificity of 0.8663. From the present study, it was possible to measure the extrusion length and meniscal height via gradation processing, with X-ray and without MRI, and to calculate the meniscal extrusion ratio, which strongly correlates with the amount of MME on MRI.

2.
Med Princ Pract ; 32(1): 71-76, 2023.
Article in English | MEDLINE | ID: mdl-36353781

ABSTRACT

OBJECTIVES: Osteoporosis patients with fragility fractures and vertebral deformities have impaired quality of life (QOL). The phase angle, an index calculated from bioelectrical impedance analysis (BIA) measurements, has been reported to be related to clinical outcomes, mortality, and QOL in various diseases. We aimed to investigate the relationship between the phase angle and QOL in patients with postmenopausal osteoporosis. METHODS: 81 female patients treated for postmenopausal osteoporosis from September 2019 to March 2020 underwent measurement of bone mineral density (BMD) by dual-energy X-ray absorptiometry, body composition by BIA, and QOL by the 36-item Short-Form Health Survey (SF-36). RESULTS: The phase angle showed significant positive correlations with physical functioning (r = 0.270, p = 0.015) and physical component summary (PCS) (r = 0.251, p = 0.024) of the SF-36. The phase angle showed significant positive correlations with appendicular skeletal muscle mass index (ASMI) (r = 0.456, p < 0.001), lumbar spine BMD (r = 0.241, p = 0.030), and femoral neck BMD (r = 0.26, p = 0.021) and a significant negative correlation with age (r = -0.526, p < 0.001). Multiple regression analysis of the factors potentially associated with SF-36 PCS showed that the phase angle (r = 7.506, p = 0.012) was a significant contributor to PCS (R2 = 0.184). CONCLUSION: The phase angle in postmenopausal osteoporotic patients was significantly related to QOL after adjusting for age, BMI, ASMI, and BMD. As the phase angle is a parameter that can be measured easily and noninvasively, it might be a useful aid for QOL assessment in osteoporotic patients.


Subject(s)
Fractures, Bone , Osteoporosis, Postmenopausal , Osteoporosis , Humans , Female , Quality of Life , Bone Density/physiology , Lumbar Vertebrae
3.
Vox Sang ; 115(8): 756-766, 2020 Nov.
Article in English | MEDLINE | ID: mdl-32394466

ABSTRACT

BACKGROUND: The low-incidence antigen Sta of the MNS system is usually associated with the GP(B-A) hybrid molecule, which carries the 'N' antigen at the N terminus. The GP(A-A) molecule with trypsin-resistant M antigen has been found in a few St(a+) individuals. MATERIALS AND METHODS: Among Japanese blood donors, we screened 24 292 individuals for the presence of St(a+) with trypsin-resistant 'N' antigen and 193 009 individuals for the presence of St(a+) with trypsin-resistant M antigen. The breakpoints responsible for the Sta antigen were analysed by sequencing the genomic DNAs. RESULTS: A total of 1001 (4·1%) individuals were identified as St(a+) with trypsin-resistant 'N' antigen. Out of 1001 individuals, 115 were selected randomly for sequencing. Two novel GYP*Sch (GYP*401) variants with new intron 3 breakpoints of GYPA were detected in three cases. Twenty-five (0·013%) individuals were identified as St(a+) with trypsin-resistant M antigen. Five individuals had the GYP(A-ψB-A) hybrid allele; two of these five individuals were GYP*Zan (GYP*101.01), and the remaining three had a novel GYP(A-ψB-A) allele with the first breakpoint in GYPA exon A3 between c.178 and c.203. Nine individuals had a novel GYP(A-E-A) allele with GYPE exon E2 and pseudoexon E3 instead of GYPA exon A2 and A3. The 11 remaining individuals had a novel GYP(A-A) allele with a 9-bp deletion that included the donor splice site of intron 3 of GYPA. CONCLUSION: Our finding on diversity of glycophorin genes responsible for Sta antigen provides evidence for further complexity in the MNS system.


Subject(s)
Blood Donors , Glycophorins/genetics , Mutation , RNA Splice Sites , Alleles , Asian People/genetics , Exons , Humans , Japan , MNSs Blood-Group System/genetics
4.
Knee ; 27(3): 838-845, 2020 Jun.
Article in English | MEDLINE | ID: mdl-32331828

ABSTRACT

BACKGROUND: Spontaneous osteonecrosis of the knee (SONK) is one of the acute knee pain disorders arising in elderly patients. The presence of knee varus alignment and the size of necrotic area have been reported as the negative prognostic factors in prior studies. However, no previous study has yet clarified the radiological analysis of the lower extremity in SONK compared with that in osteoarthritis. The purpose of this study was therefore to identify the radiographic findings of the lower extremity in SONK. METHODS: Sixty-three knees of Kellgren-Lawrence classification grade 1 or 2 without any trauma treated between April 2012 and March 2014 were enrolled in this study. These knees were divided into two groups according to their magnetic resonance imaging (MRI) findings: SONK group (31 knees) and OA group (32 knees). Using a long leg standing X-ray, femorotibial angle (FTA), mechanical axis deviation (MAD), mechanical lateral distal femoral angle (mLDFA), medial proximal tibial angle (MPTA) and joint line convergent angle (JLCA) were compared between groups. Correlation between each parameter and the width ratio (WR) of the necrotic lesion were analyzed. RESULTS: FTA, MAD, MPTA and JLCA showed significant differences between the SONK and OA groups. In the SONK group, FTA was positively correlated with WR, and, MAD and MPTA was negatively correlated with WR. CONCLUSIONS: Compared with OA, SONK is associated with a significantly larger varus deformity at the proximal tibia, and larger joint play in the coronal plane.


Subject(s)
Lower Extremity/diagnostic imaging , Osteoarthritis, Knee/diagnostic imaging , Osteonecrosis/diagnostic imaging , Aged , Aged, 80 and over , Female , Femur , Humans , Knee Joint , Magnetic Resonance Imaging , Male , Middle Aged , Radiography , Retrospective Studies , Sensitivity and Specificity , Standing Position , Tibia
5.
J Orthop Sci ; 24(3): 400-403, 2019 May.
Article in English | MEDLINE | ID: mdl-30424928

ABSTRACT

BACKGROUND: We sought to evaluate the hip abduction strength in patients before and after lumbar surgery. MATERIALS AND METHODS: Eighty-four patients (51 males and 33 females) undergoing surgery for lumbar disc herniation or lumbar canal stenosis were selected. Mean age was 64.7 ± 13.8 years. Seven patients (8.3%) had surgery at multiple levels, including L2-L3 (group A), 27 (32.1%) patients had surgery at multiple levels including L3-L4 (group B), 32 (38.1%) patients had surgery at the L4-L5 level only (group C), and 18 (21.4%) patients had surgery at the L5-S1 level only (group D). Hip abduction strength was measured in the 84 patients preoperatively and in 49 patients postoperatively. RESULTS: In all patients, preoperative mean hip abduction strength on the symptomatic side and the asymptomatic side was 71.4 ± 34.5 N and 90.7 ± 36.5 N, respectively (p = 0.0008). In groups A and B, there were no significant differences between the mean hip abduction strength on the symptomatic and contralateral side. In group C, those on the symptomatic and contralateral side were 68.0 ± 33.5 N and 89.3 ± 34.8 N, respectively (p = 0.0181). In group D, those on the symptomatic and contralateral side were 74.3 ± 42.4 N and 101.7 ± 44.7 N, respectively (p = 0.0314). In the 49 patients of all groups that could be measured postoperatively, there were no significant differences between the mean hip abduction strength on both sides. CONCLUSIONS: It was confirmed that the gluteus medius, which was main hip abductor, was mainly innervated by L5 and its mean strength significantly improved postoperatively. The possibility of improvement of hip abduction strength, especially with unchanged tibialis anterior strength, could be very useful for operative decisions.


Subject(s)
Hip/physiopathology , Intervertebral Disc Displacement/surgery , Lumbar Vertebrae , Muscle Strength/physiology , Range of Motion, Articular/physiology , Spinal Stenosis/surgery , Aged , Female , Humans , Intervertebral Disc Displacement/complications , Intervertebral Disc Displacement/physiopathology , Male , Middle Aged , Muscle, Skeletal/physiopathology , Recovery of Function , Retrospective Studies , Spinal Stenosis/complications , Spinal Stenosis/physiopathology , Treatment Outcome
6.
Arthroscopy ; 34(7): 2207-2217, 2018 07.
Article in English | MEDLINE | ID: mdl-29730221

ABSTRACT

PURPOSE: To determine the visualization rate of the anterolateral ligament (ALL) in uninjured and anterior cruciate ligament (ACL)-deficient knees using 3-dimensional (3D) magnetic resonance imaging (MRI) and to characterize the spectrum of ALL injury observed in ACL-deficient knees, as well as determine the interobserver and intraobserver reliability of a 3D MRI classification of ALL injury. METHODS: A total of 100 knees (60 ACL deficient and 40 uninjured) underwent 3D MRI. The ALL was evaluated by 2 blinded orthopaedic surgeons. The ALL was classified as follows: type A, continuous, clearly defined low-signal band; type B, warping, thinning, or iso-signal changes; and type C, without clear continuity. The comparison between imaging performed early after ACL injury (<1 month) and delayed imaging (>1 month) was evaluated, as was intraobserver and interobserver reliability. RESULTS: Complete visualization of the ALL was achieved in all uninjured knees. In the ACL-deficient group, 24 knees underwent early imaging, with 87.5% showing evidence of ALL injury (3 normal, or type A, knees [12.5%], 18 type B [75.0%], and 3 type C [12.5%]). The remaining 36 knees underwent delayed imaging, with 55.6% showing evidence of injury (16 type A [44.4%], 18 type B [50.0%], and 2 type C [5.6%]). The difference in the rate of injury between the 2 groups was significant (P = .03). Multivariate analysis showed that the delay from ACL injury to MRI was the only factor (negatively) associated with the rate of injury to the ALL. Interobserver reliability and intraobserver reliability of the classification of ALL type were good (κ = 0.86 and κ = 0.93, respectively). CONCLUSIONS: Three-dimensional MRI allows full visualization of the ALL in all normal knees. The rate of injury to the ALL in acutely ACL-injured knees identified on 3D MRI is higher than previous reports using standard MRI techniques. This rate is significantly higher than the rate of injury to the ALL identified on delayed imaging of ACL-injured knees. LEVEL OF EVIDENCE: Level IV, diagnostic, case-control study.


Subject(s)
Anterior Cruciate Ligament Injuries/diagnostic imaging , Anterior Cruciate Ligament/diagnostic imaging , Knee Joint , Ligaments, Articular/diagnostic imaging , Adolescent , Adult , Anterior Cruciate Ligament/pathology , Anterior Cruciate Ligament/surgery , Anterior Cruciate Ligament Injuries/pathology , Anterior Cruciate Ligament Injuries/surgery , Case-Control Studies , Double-Blind Method , Female , Humans , Imaging, Three-Dimensional , Ligaments, Articular/pathology , Ligaments, Articular/surgery , Magnetic Resonance Imaging , Male , Middle Aged , Predictive Value of Tests , Reproducibility of Results , Young Adult
7.
Nihon Hoshasen Gijutsu Gakkai Zasshi ; 72(5): 416-23, 2016 May.
Article in Japanese | MEDLINE | ID: mdl-27211087

ABSTRACT

Anterolateral ligament (ALL) is one of the lateral structures in the knee that contributes to the internal rotational stability of tibia. ALL has been referred to in some recent reports to re-emphasize its importance. We visualized the ALL on 3D-MRI in 32 knees of 27 healthy volunteers (23 male knees, 4 female knees; mean age: 37 years). 3D-MRIs were performed using 1.5-T scanner [T(2) weighted image (WI), SPACE: Sampling Perfection with Application optimized Contrast using different flip angle Evolutions] in the knee extended positions. The visualization rate of the ALL, the mean angle to the lateral collateral ligament (LCL), and the width and the thickness of the ALL at the joint level were investigated. The visualization rate was 100%. The mean angle to the LCL was 10.6 degrees. The mean width and the mean thickness of the ALL were 6.4 mm and 1.0 mm, respectively. The ALL is a very thin ligament with a somewhat oblique course between the lateral femoral epicondyle and the mid-third area of lateral tibial condyle. Therefore, the slice thickness and the slice angle can easily affect the ALL visualization. 3D-MRI enables acquiring thin-slice imaging data over a relatively short time, and arbitrary sections aligned with the course of the ALL can later be selected.


Subject(s)
Ligaments, Articular/anatomy & histology , Magnetic Resonance Imaging/methods , Adult , Female , Humans , Imaging, Three-Dimensional/methods , Knee Joint , Male , Phantoms, Imaging
8.
Ups J Med Sci ; 121(3): 170-3, 2016 Aug.
Article in English | MEDLINE | ID: mdl-27228191

ABSTRACT

BACKGROUND: Multiple factors are involved in the development of atypical femoral fractures, and excessive curvature of the femur is thought to be one of them. However, the pathogenesis of femoral curvature is unknown. We evaluated the influence of factors related to bone metabolism and posture on the development of femoral curvature. METHODS: A total of 139 women participated in the present study. Curvatures were measured using antero-posterior and lateral radiography of the femur. We evaluated some bone and vitamin D metabolism markers in serum, the bone mineral density (BMD), lumbar spine alignment, and pelvic tilt. RESULTS: We divided the women into two groups, curved and non-curved groups, based on the average plus standard deviation as the cut-off between the groups. When univariate logistic regression analysis was performed to detect factors affecting femoral curvature, the following were identified as indices significantly affecting the curvature: age of the patients, serum concentrations of calcium, intact parathyroid hormone, pentosidine, homocysteine and 25-hydroxyvitamin D (25(OH)D), and BMD of the proximal femur (P < 0.05) both in the lateral and anterior curvatures. When we used multivariate analyses to assess these factors, only 25(OH)D and age (lateral and anterior standardized odds ratio: 0.776 and 0.385, and 2.312 and 4.472, respectively) affected the femoral curvature (P < 0.05). CONCLUSION: Femoral curvature is strongly influenced by age and serum vitamin D.


Subject(s)
Femoral Fractures/etiology , Femur/abnormalities , Vitamin D/analogs & derivatives , Aged , Aged, 80 and over , Arginine/analogs & derivatives , Arginine/blood , Bone Density , Calcium/blood , Female , Femoral Fractures/diagnostic imaging , Femoral Fractures/ethnology , Femur/diagnostic imaging , Homocysteine/blood , Humans , Japan , Lumbar Vertebrae , Lysine/analogs & derivatives , Lysine/blood , Middle Aged , Multivariate Analysis , Odds Ratio , Parathyroid Hormone/blood , Regression Analysis , Vitamin D/blood , Vitamin D Deficiency/complications
9.
Biomed Res ; 37(2): 101-15, 2016.
Article in English | MEDLINE | ID: mdl-27108880

ABSTRACT

5-hydroxytriptamine (5-HT: serotonin) is an important transmitter that causes vessel constriction, although few studies have examined the effect of 5-HT on venous smooth muscles. The intracellular Ca(2+) concentration ([Ca(2+)]i) plays an essential role in stimulus-response coupling in numerous tissue/cells including vascular smooth muscle cells. The present study was performed to examine whether differences between arteries and veins in the response to 5-HT can be detected under confocal microscope with respect to [Ca(2+)]i dynamics. In posterior ciliary arteries of rats, 5-HT induced a [Ca(2+)]i increase. The 5-HT-induced responses were caused by both Ca(2+) influx and mobilization. Agonist and antagonist experiments revealed that arterial smooth muscles possess 5-HT1a, 1b, 2 (Gprotein-coupled type) and 5-HT3 (ion channel type) receptors, and that 5-HT2 in particular plays a major role in these responses. For vorticose veins, the 5-HT-induced responses were also caused by both Ca(2+) influx and mobilization. However, the cAMP dependent pathway (5-HT4-7) was found to be significant in vasocontraction with respect to 5-HT in these vessels. Thus, Ca(2+) mobilization was induced by 5-HT2 and 5-HT4-7 in a vessel-dependent manner, whereas Ca(2+) influx universally was induced by 5-HT3. These results indicate that the posterior ciliary arteries and vorticose veins in the same tissue might differ greatly in their responses to stimulus.


Subject(s)
Calcium Signaling/drug effects , Calcium/metabolism , Ciliary Arteries/cytology , Ciliary Arteries/drug effects , Myocytes, Smooth Muscle/drug effects , Myocytes, Smooth Muscle/metabolism , Serotonin/pharmacology , Varicose Veins/drug therapy , Animals , Ciliary Arteries/metabolism , Intracellular Space/metabolism , Microscopy, Confocal , Molecular Imaging , Rats
10.
Biomed Res ; 37(1): 37-49, 2016.
Article in English | MEDLINE | ID: mdl-26912139

ABSTRACT

Adenosine 5'-triphosphate (ATP) can act as an extracellular signal that regulates various cellular functions. The present study aimed to determine which purinoceptors play a role in ATP-induced changes in intracellular Ca(2+) ([Ca(2+)]i) and amylase secretion in mouse parotid glands. ATP induced a steep increase in [Ca(2+)]i in acinar cells. The removal of extracellular Ca(2+) or the use of Ca(2+) channel blockers slightly inhibited this increase. Inhibition of PLCγ by U73122 and of IP3 by xestospongin C did not completely block this increase. The purinoceptor antagonists suramin and reactive blue-2 strongly inhibited the ATP-induced changes in [Ca(2+)]i. 2-MeSATP induced a strong increase in [Ca(2+)]i, while Bz-ATP induced a small [Ca(2+)]i increase, and UTP and α,ß-MeATP had no effect. The potency order of ATP analogs (2-MeSATP > ATP >> UTP) suggested that P2Y1 and P2Y12 play a significant role in the cellular response to ATP. RT-PCR revealed that P2X2,4,7 and P2Y1,2,10,12,14 were expressed in acinar cells. Ca(2+)-dependent exocytotic secretion of amylase was detected in parotid glands. These findings indicated that ATP activates P2Y receptors more than P2X receptors at low concentrations. Thus, P2Y receptors were found to be the main receptors involved in Ca(2+)-related cell homeostasis and amylase secretion in mouse parotid glands.


Subject(s)
Acinar Cells/metabolism , Adenosine Triphosphate/metabolism , Amylases/metabolism , Calcium/metabolism , Parotid Gland/cytology , Parotid Gland/metabolism , Receptors, Purinergic P2Y/metabolism , Acinar Cells/drug effects , Animals , Calcium Signaling/drug effects , Enzyme Activation , Gene Expression , Intracellular Space/metabolism , Mice , Purinergic P2Y Receptor Agonists/pharmacology , Purinergic P2Y Receptor Antagonists/pharmacology , RNA, Messenger/genetics , Receptors, Purinergic P2Y/genetics
11.
Biomed Res ; 37(1): 73-6, 2016.
Article in English | MEDLINE | ID: mdl-26912142

ABSTRACT

The purpose of this study was to compare postcontraction hyperemia after electrical stimulation between patients with upper extremity paralysis caused by upper motor neuron diseases and healthy controls. Thirteen healthy controls and eleven patients with upper extremity paralysis were enrolled. The blood flow in the basilic vein was measured by ultrasound before the electrical stimulation of the biceps brachii muscle and 30 s after the stimulation. The stimulation was performed at 10 mA and at a frequency of 70 Hz for 20 s. The mean blood flow in the healthy control group and in upper extremity paralysis group before the electrical stimulation was 60 ± 20 mL/min (mean ± SD) and 48 ± 25 mL/min, respectively. After the stimulation, blood flow in both groups increased to 117 ± 23 mL/min and 81 ± 41 mL/min, respectively. We show that it is possible to measure postcontraction hyperemia using an ultrasound system. In addition, blood flow in both groups increased after the electrical stimulation because of postcontraction hyperemia. These findings suggest that evaluating post contraction hyperemia in patients with upper extremity paralysis can assess rehabilitation effects.


Subject(s)
Electric Stimulation , Hyperemia/physiopathology , Muscle Contraction , Muscle, Skeletal/blood supply , Muscle, Skeletal/physiology , Arm/blood supply , Arm/physiopathology , Case-Control Studies , Electric Stimulation Therapy , Humans , Muscle, Skeletal/physiopathology , Paralysis/etiology , Paralysis/physiopathology , Paralysis/therapy , Regional Blood Flow
12.
Biomed Res ; 33(2): 89-96, 2012 Apr.
Article in English | MEDLINE | ID: mdl-22572383

ABSTRACT

Hemiplegia is a common sequel of stroke and assisted living care is needed in many cases. The purpose of this study was to evaluate the effect of using surface electrode stimulation device in rehabilitation, in terms of functional improvement in upper limb and the changes in brain activation related to central nervous system reconstruction. Five patients with chronic hemiplegia received electrical stimulation therapy using the orthosis-type surface electrode stimulation device for 12 weeks. Training time was 30 min/day for the first weeks, and increased 30 min/day in every 4 weeks. Upper limb outcome measures included Brunnstrom stage, range of motion, Fugl-Meyer assessment and manual function test. Brain activation was measured using functional MRI. After therapy with therapeutic electrical stimulation (TES) for 12 weeks upper limb function improved in all cases. The results of brain activation showed two patterns. In the first, the stimulation produced an activity in the bilateral somatosensory cortices (SMC), which was seen to continue over time. The second, activation was bilateral and extensive before stimulation, but localized to the SMC after intervention. Treatment with TES using an orthosis-type electrode stimulation device improves upper limb function in chronic hemiplegia patients. The present findings suggest that there are not only efferent but also afferent effects that may promote central nervous system remodeling.


Subject(s)
Arm/physiopathology , Cerebral Cortex/physiopathology , Electric Stimulation Therapy , Hemiplegia/therapy , Adult , Aged , Analysis of Variance , Chronic Disease , Female , Hemiplegia/physiopathology , Humans , Magnetic Resonance Imaging , Male , Middle Aged , Recovery of Function , Severity of Illness Index , Treatment Outcome
13.
J Biol Chem ; 282(13): 9895-9901, 2007 Mar 30.
Article in English | MEDLINE | ID: mdl-17283079

ABSTRACT

Krüppel-like factor 5 (KLF5) is a transcription factor important in regulation of the cardiovascular response to external stress. KLF5 regulates pathological cell growth, and its acetylation is important for this effect. Its mechanisms of action, however, are still unclear. Analysis in KLF5-deficient mice showed that KLF5 confers apoptotic resistance in vascular lesions. Mechanistic analysis further showed that it specifically interacts with poly(ADP-ribose) polymerase-1 (PARP-1), a nuclear enzyme important in DNA repair and apoptosis. KLF5 interacted with a proteolytic fragment of PARP-1, and acetylation of KLF5 under apoptotic conditions increased their affinity. Moreover, KLF5 wild-type (but not a non-acetylatable point mutant) inhibited apoptosis as induced by the PARP-1 fragment. Collectively, we have found that KLF5 regulates apoptosis and targets PARP-1, and further, for acetylation to regulate these effects. Our findings thus implicate functional interaction between the transcription factor KLF5 and PARP-1 in cardiovascular apoptosis.


Subject(s)
Apoptosis/physiology , Cardiovascular System/enzymology , Kruppel-Like Transcription Factors/physiology , Poly(ADP-ribose) Polymerases/physiology , 3T3 Cells , Acetylation , Animals , Apoptosis/genetics , Cardiovascular System/metabolism , Cardiovascular System/physiopathology , Cell Line , HeLa Cells , Humans , Kruppel-Like Transcription Factors/metabolism , Male , Mice , Mice, Knockout , Point Mutation , Poly (ADP-Ribose) Polymerase-1 , Poly(ADP-ribose) Polymerases/metabolism
14.
J Biol Chem ; 279(1): 70-6, 2004 Jan 02.
Article in English | MEDLINE | ID: mdl-14573617

ABSTRACT

The transcription factor Krüppel-like factor 5 (KLF5) and its genetically downstream target gene platelet-derived growth factor-A (PDGF-A) chain are key factors in regulation of cardiovascular remodeling in response to stress. We show that KLF5 mediates a novel distinct delayed persistent induction of PDGF-A chain in response to the model agonist, phorbol ester, through a cis-element previously shown to mediate phorbol ester induction on to PDGF-A chain through the early growth response factor (Egr-1). Interestingly, the nuclear factor-kappaB (NF-kappaB) p50 subunit further cooperatively activates PDGF-A chain through protein-protein interaction with KLF5 but not Egr-1. RNA interference analysis confirmed that KLF5 and p50 are important for induction of PDGF-A chain. Collectively, we identify a novel regulatory pathway in which PDGF-A chain gene expression, under the control of KLF5, is cooperatively activated by the NF-kappaB p50 subunit and a pathophysiological stimulus.


Subject(s)
NF-kappa B/metabolism , Platelet-Derived Growth Factor/genetics , Trans-Activators/metabolism , Base Sequence , Binding Sites , DNA Primers , Genes, Reporter , HeLa Cells , Humans , Kruppel-Like Transcription Factors , Luciferases/genetics , Promoter Regions, Genetic , Protein Subunits/metabolism , Recombinant Proteins/chemistry , Recombinant Proteins/metabolism , Trans-Activators/chemistry , Trans-Activators/genetics , Transcriptional Activation , Transfection , Zinc Fingers
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