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PubMed1998

Inhibition of matrix metalloproteinase 2 maturation and HT1080 invasiveness by a synthetic furin inhibitor.

The close correlation observed between matrix metalloproteinase 2 (MMP-2) activation and metastatic progression in various tumors suggests that MMP-2 is a 'master switch' triggering tumor spread. Recently, membrane type 1 MMP (MT1-MMP) was identified as a potential physiological activator of MMP-2. Like all other MMPs, MT1-MMP possesses a pro-domain which must be removed for the enzyme to acquire its catalytic potential. The presence of a typical recognition motif (RXKR) for the furin-like convertases at the end of its pro-domain suggests a potential role for these proteinases in MT1-MMP processing. In order to evaluate the implication of furin in pro-MT1-MMP processing, we treated HT1080 cells with a synthetic furin inhibitor and monitored their ability to activate pro-MMP-2 as well as their invasive potential. Our results demonstrated that the furin inhibitor decreased pro-MT1-MMP processing as well as pro-MMP-2 activation and cell invasiveness. Therefore, our data bring further evidence that furin is a key factor in the maturation of MMPs associated with the invasive and metastatic potential of tumor cells.

Amino Acid Chloromethyl Ketones↗
PubMed1991

The construction of a scored neonatal neurological examination for assessment of neurological integrity in full-term neonates.

We describe the construction of a scored form for the neurological examination of the full-term neonate. Extensive data analyses were obtained from a large sample of neonatal neurological examinations performed by one examiner (MSP). Examinations were used from neonates with ages less than or equal to 48 hours (n = 727) and 72 hours to 1 week (n = 510) with gestational ages greater than or equal to 37 weeks. Forty-four items from several neonatal assessments were used in these neurological examinations. Further subdivision yielded a total of 65 items. Correlations were obtained for the 65 items. We factored the matrix of these correlations, using several solutions of factor analysis. Thirty-two items were thus grouped and pruned into seven dimensions (factors) to provide a scorable neonatal neurological examination (Neoneuro) with an internal consistency or reliability of 0.80. From the total scores, cut points are recommended for categories of normality/abnormality: normal, mildly abnormal, moderately abnormal, and severely abnormal. This scoring system is well-based both theoretically and psychometrically. The quantified computer-compatible scoring system permits evaluation of individual neonates, as well as comparison of samples of neonates on item scores, subscores (factor scores), and total scores. Such quantification will permit documentation of the natural history of specific abnormalities and the evaluation of various therapies.

Brain Damage, Chronic↗
PubMed2006

Two-electron distribution functions and short-range electron correlations of atoms and molecules by first principles T-matrix calculations.

The accurate first principles description of the correlations between electrons has been a topic of interest in molecular physics. We have reported in our previous paper [J. Chem. Phys. 123, 144112 (2005)] that the T matrix, which is the ladder diagrams up to the infinite order, can accurately represent the short-range electron correlations while calculating the double ionization energy spectra of atoms and molecules. In this paper, we calculate the two-electron distribution functions of real systems (Ar, CO, CO(2), and C(2)H(2)) from the eigenvalue equation associated with the Bethe-Salpeter equation for the T matrix by beginning with the local density approximation of the density functional theory and the GW approximation. We found that when the interelectron distance is very small, the Coulomb hole appears between antiparallel spin electrons due to the short-range repulsive Coulomb interaction. The resulting two-electron distribution functions clearly show the Coulomb hole.

Journal Article↗
PubMed1997

Increased expression of integrins on fibroblast-like synoviocytes from rheumatoid arthritis in vitro correlates with enhanced binding to extracellular matrix proteins.

OBJECTIVE: To compare in vitro expression of beta 1, beta 3, and beta 4 integrins in normal fibroblast-like synoviocytes (FBS) and in FBS from rheumatoid arthritis (RA) synovium and to investigate the adhesion of normal FBS and RA-FBS to the integrin binding extracellular matrix (ECM) proteins: collagen type IV, fibronectin, laminin, and tenascin. METHODS: Expression of integrin receptors of cultured FBS was detected by flow cytometry. Attachment of FBS to ECM proteins was quantified by adhesion assays. Inhibition studies were performed using monoclonal antibodies to the integrin subunits. RESULTS: Compared with normal FBS, RA-FBS showed increased expression of alpha 1 to alpha 6, beta 1, and beta 4 integrin subunits and enhanced binding of ECM proteins. Binding to ECM proteins was partly or completely blocked by an anti-beta 1 integrin antibody and antibodies to alpha 3, alpha 5, and alpha 6 integrin subunits. The blocking efficiency was significantly (P < 0.05) higher in RA-FBS than in normal FBS. CONCLUSIONS: The enhanced expression of the beta 1 integrin receptors on cultured RA-FBS correlated with increased attachment to ECM proteins. Adhesion of normal and RA-FBS to ECM proteins is mediated through beta 1 integrin receptors. Therefore, the tight binding of rheumatoid FBS to the matrix via beta 1 integrins might play a role in ECM remodelling in the rheumatoid process in vivo.

Arthritis, Rheumatoid↗
PubMed1993

ANB skeletal types correlated to facial morphology: Euclidean distance matrix analysis.

Pretreatment lateral skull radiographs of 145 patients aged 7 to 20 years are classified according to an ANB-angle reading corrected for the position of the maxilla and rotation of the jaw. The Euclidean distance matrix analysis is applied to compare the overall facial morphology between Classes I and II. This method differentiates between size and shape and localizes those areas that differ the most. Statistically significant different facial morphologies were demonstrated in the 32 patients aged 15 years or more. The younger patients with skeletal Classes I and II did not possess these different morphological characteristics. The results show that standard cephalometric classification criteria do not always correlate to actual differences in the overall facial morphology.

Adolescent↗
PubMed2006

Joint capsule matrix turnover in a rabbit model of chronic joint contractures: Correlation with human contractures.

To evaluate changes in matrix molecules of the joint capsule, the right knees of 24 skeletally mature female NZW rabbits were immobilized while the contralateral limb served as an unoperated control. The immobilization was discontinued at 8 weeks and the rabbits were divided among four groups (n = 6) based on the number of weeks the right knees were remobilized: 0, 8, 16, or 32. Three rabbits (six knees) that did not have operations provided normal control joint capsules. The mRNA levels for collagen types I, II, and III, and MMP-1 and -13 were significantly increased in the joint capsules of the contracture knees in all groups when compared to normal and contralateral limb joint capsules. In contrast, the mRNA levels for TIMP-1, -2, and -3 were decreased in the joint capsules of the contracture knees in all groups when compared to normal and contralateral limb joint capsules. The mRNA levels for lumican and decorin were increased in the joint capsules of the contracture knees in all groups when compared to normal capsules. Many of the changes observed in this animal model are similar to those observed in human joint capsules from posttraumatic elbow contractures, supporting the value of this rabbit model.

Animals↗
PubMed2005

Plasma levels of matrix metalloproteinase-2 and tissue inhibitor of metalloproteinase-1 correlate with disease stage and survival in colorectal cancer patients.

PURPOSE: The matrix metalloproteinases and their inhibitors are known to be involved in the process of tumor invasion and progression. Our objective was to investigate the potential diagnostic and prognostic value of plasma matrix metalloproteinase-2 and -9 and tissue inhibitor of metalloproteinase-1 in colorectal cancer. METHODS: Gelatinase bioactivity and immunoreactivity of pro-matrix metalloproteinase-2 and -9, tissue inhibitor of metalloproteinase-1, and carcinoembryonic antigen were determined simultaneously in preoperative plasma and serum of colorectal cancer patients (n = 94) and in healthy controls (n = 51). RESULTS: Plasma pro-matrix metalloproteinase-2 levels were lower in colorectal cancer patients (P < 0.0001) than in controls, and its gelatinolytic activity revealed an inverse correlation with adverse clinicopathologic parameters, such as lymph node involvement (P = 0.017), stage (0, I, II vs. III, IV; P = 0.012), and the carcinoembryonic antigen level (P = 0.016). Pro-matrix metalloproteinase-9 levels did not differ between patients and controls. Pro-matrix metalloproteinase-2 gelatinolytic activity showed potential value in colorectal cancer diagnosis, identifying patients with 70 percent sensitivity at 95 percent specificity. Pro-matrix metalloproteinase-9, tissue inhibitor of metalloproteinase-1, and carcinoembryonic antigen all showed lower sensitivities. Combining pro-matrix metalloproteinase-2 and tissue inhibitor of metalloproteinase-1 measurements increased the sensitivity significantly to 84 percent. With respect to prognosis, tissue inhibitor of metalloproteinase-1 showed value in predicting disease outcome in our patient group, whereas pro-matrix metalloproteinase-2 and -9 did not. The combination of tissue inhibitor of metalloproteinase-1 and carcinoembryonic antigen was better in predicting three-year survival than tissue inhibitor of metalloproteinase-1 alone, but it remains to be determined if the combination would be a better marker for survival than carcinoembryonic antigen alone. CONCLUSIONS: Low pro-matrix metalloproteinase-2 levels and high tissue inhibitor of metalloproteinase-1 levels correlate with parameters of colorectal cancer disease. These correlations may be used in the search for new markers in colorectal cancer diagnosis and prognosis.

Adult↗
PubMed2001

LC-MS/MS signal suppression effects in the analysis of pesticides in complex environmental matrices.

The application of LC separation and mobile phase additives in addressing LC-MS/MS matrix signal suppression effects for the analysis of pesticides in a complex environmental matrix was investigated. It was shown that signal suppression is most significant for analytes eluting early in the LC-MS analysis. Introduction of different buffers (e.g. ammonium formate, ammonium hydroxide, formic acid) into the LC mobile phase was effective in improving signal correlation between the matrix and standard samples. The signal improvement is dependent on buffer concentration as well as LC separation of the matrix components. The application of LC separation alone was not effective in addressing suppression effects when characterizing complex matrix samples. Overloading of the LC column by matrix components was found to significantly contribute to analyte-matrix co-elution and suppression of signal. This signal suppression effect can be efficiently compensated by 2D LC (LC-LC) separation techniques. The effectiveness of buffers and LC separation in improving signal correlation between standard and matrix samples is discussed.

Buffers↗
PubMed1999

Selective loss of PMA-stimulated expression of matrix metalloproteinase 1 in HaCaT keratinocytes is correlated with the inability to induce mitogen-activated protein family kinases.

Many cell types, including fibroblasts and primary keratinocytes, increase matrix metalloproteinase 1 (MMP-1) production in response to agonists such as growth factors and phorbol esters. However, the spontaneously transformed human keratinocyte cell line HaCaT, although it increases MMP-1 production in response to epidermal growth factor (EGF), does not respond similarly to stimulation with PMA. This phenomenon occurs even though HaCaT cells remain proliferatively responsive to both agonists, suggesting a HaCaT-specific defect in a PMA-mediated signal transduction pathway. Using an inside-out approach to elucidate the source of this defect, we found that EGF, but not PMA, stimulated MMP-1 promoter activity in transiently transfected HaCaT keratinocytes. In addition, an assessment of fibroblast and HaCaT c-fos and c-jun gene expression after exposure to EGF and PMA showed that although both agonists increased the expression of c-fos and c-jun mRNA in fibroblasts, only EGF did so in HaCaT keratinocytes. Finally, we looked at the activation of mitogen-activated protein (MAP) family kinases after stimulation with EGF or PMA and found that both agonists increased the phosphorylation and activation of fibroblast extracellular signal-regulated protein kinase and c-Jun N-terminal kinase, but only EGF activated the same kinase activities in HaCaT cells. Further, the EGF-mediated increase in MMP-1 gene expression was inhibited by the MAP kinase/ERK kinase (MEK)-specific inhibitor PD98059 and the p38 kinase-specific inhibitor SB203580. Our evidence indicates that although HaCaT MAP kinases are functional, they are not properly regulated in response to the activation of protein kinase C, and that the defect that bars HaCaT MMP-1 expression in response to stimulation with PMA lies before MAP kinase activation.

Calcium-Calmodulin-Dependent Protein Kinases↗
PubMed1975

Population genetics of euphydryas butterflies. I Genetic variation and the neutrality hypothesis.

Twenty-one populations of the checkerspot butterfly, Euphydryas editha, and ten populations of Euphydryas chalcedona were sampled for genetic variation at eight polymorphic enzyme loci. Both species possessed loci that were highly variable from population to population and loci that were virtually identical across all populations sampled. Our data indicate that the neutrality hypothesis is untenable for the loci studied, and therefore selection is indicated as the major factor responsible for producing these patterns. Thorough ecological work allowed gene flow to be ruled out (in almost all instances) as a factor maintaining similar gene frequencies across populations. The Lewontin-Krakauer test indicated magnitudes of heterogeneity among standardized variances of gene frequencies inconsistent with the neutrality hypothesis. The question of whether or not to correct this statistic for sample size is discussed. Observed equitability of gene frequencies of multiple allelic loci was found to be greater than that predicted under the neutrality hypothesis. Genetic differentiation persisting through two generations was found between the one pair of populations known to exchange significant numbers of individuals per generation. Two matrices of genetic distance between populations, based on the eight loci sampled, were found to be significantly correlated with a matrix of environmental distance, based on measures of fourteen environmental parameters. Correlations between gene frequencies and environmental parameters, results of multiple regression analysis, and results of principle component analysis showed strong patterns of association and of "explained" variation. The correlation analyses suggest which factors might be further investigated as proximate selective agents.

Animals↗
PubMed2005

Significance of matrix metalloproteinase 9 and CD34 expressions in esophageal carcinoma: correlation with DNA content.

BACKGROUND: Esophageal carcinoma is common in many countries, and it is characterized by poor prognosis and rapid clinical progression with a high frequency of lymph node metastasis and recurrence. The present study was carried out to evaluate the correlation between vascular endothelial cell marker (CD34), matrix metalloproteinase type 9 (MMP9), and DNA content in esophageal carcinoma. METHODS: A total of 38 patients were classified with histopathologic examination as 8 cases with adenocarcinoma, 24 cases with squamous cell carcinoma, and the last 6 cases with undifferentiated carcinoma. The obtained results of the patient group were compared with the results of 6 cases with proven normal esophageal mucosa as a control group. The samples of patients and controls were subjected to immunohistochemical evaluation of CD34 and MMP9 expression along with DNA index determination using flow cytometry. RESULTS: There was a significant difference between patients and normal cases in DNA index, CD34, and MMP9 pattern (P = 0.003, <0.001, and 0.002, respectively). DNA index was positively correlated with MMP9 (r = 0.574, P < 0.001) and with CD34 (r = 0.562, P < 0.001). MMP9 was correlated with CD34 (r = 0.55, P < 0.001). A significant difference was found in both microvessel density and MMP9 expression with respect to tumor grade and stage. The microvessel density in patients with highly positive staining for MMP9 was higher than in those with negative and weak staining for MMP9 (P = 0.002). CONCLUSION: The analysis of DNA content along with detection of CD34 and MMP9 in esophageal cancer can successfully differentiate the different pathologic lesions and hence can be used powerfully in disease prognosis reflecting valuable information about the aggressiveness and activity of those lesions.

Adenocarcinoma↗
PubMed1986

The interphotoreceptor matrix in RCS rats: histochemical analysis and correlation with the rate of retinal degeneration.

We have previously demonstrated with histochemical digestions that a spatial heterogeneity exists in the interphotoreceptor matrix (IPM) of the normal rat retina. The apical outer segment zone adjacent to the pigment epithelium is mostly sialoglycoconjugates, and the basal outer segment zone appears to consist largely of chondroitin sulfates A and C, with sialogylcoconjugates in low concentration (Porrello and LaVail, in press). Although the RCS rat with inherited retinal dystrophy is missing the apical zone of IPM in the posterior retina, it has an abnormally high concentration of IPM in the basal zone and a concentrated apical zone in the far peripheral retina (LaVail, Pinto and Yasumura, 1981). We have attempted to characterize the IPM histochemically in these two regions in the RCS rat. Using the same digestive procedures which remove hyaluronic acid, chondroitin sulfates A and C, and sialoglycoconjugates, we find that the excessive basal IPM accumulation in the RCS retina appears to be composed in large part of chondroitin sulfates A and C, whereas the peripheral apical zone contains little or no chondroitin sulfates A and C. Furthermore, little or no sialoglycoconjugates are present in the basal zone, and the peripheral apical zone is composed predominantly of sialoglyconjugates. Thus, the IPM in the RCS rat possesses the same regional heterogeneity as that found in the normal rat IPM. Changes in IPM staining during the progression of retinal degeneration were examined in the eyes of both pink-eyed RCS and pigmented RCS-p+ rats. IPM staining was characterized by progressive condensation of the initially abundant basal stain into a thin band adjacent to the outer limiting membrane. The loss was concomitant with the reduction in photoreceptor inner-segment length and integrity, precisely matching the central to peripheral gradient and hemispheric differences in the rate of photoreceptor degeneration in these animals. This suggests that photoreceptor cells produce some or all of the chondroitin sulfates of the IPM. The peripheral apical staining was lost rapidly between days 30-40, which correlates closely with the loss of interstitial retinol-binding protein as described by others.

Animals↗
PubMed2006

Multireference correlation in long molecules with the quadratic scaling density matrix renormalization group.

We have devised a local ab initio density matrix renormalization group algorithm to describe multireference correlations in large systems. For long molecules that are extended in one of their spatial dimensions, we can obtain an exact characterization of correlation, in the given basis, with a cost that scales only quadratically with the size of the system. The reduced scaling is achieved solely through integral screening and without the construction of correlation domains. We demonstrate the scaling, convergence, and robustness of the algorithm in polyenes and hydrogen chains. We converge to exact correlation energies (in the sense of full configuration interaction, with 1-10 microE(h) precision) in all cases and correlate up to 100 electrons in 100 active orbitals. We further use our algorithm to obtain exact energies for the metal-insulator transition in hydrogen chains and compare and contrast our results with those from conventional quantum chemical methods.

Journal Article↗
PubMed2000

Coexpression of integrin alpha(v)beta3 and matrix metalloproteinase-2 (MMP-2) coincides with MMP-2 activation: correlation with melanoma progression.

Tumor cell invasion and metastasis formation depend on both adhesive and proteolytic mechanisms. Previous studies have shown that expression of matrix metalloproteinase-2 and integrin alphavbeta3 correlate with melanoma progression. Recently, direct binding of matrix metalloproteinase-2 to alpha(v)beta3 was implicated in presenting activated matrix metalloproteinase-2 on the cell surface of invasive cells. In this study we investigated this, using the highly metastatic, alpha(v)beta3-negative melanoma cell lines MV3 and BLM, their beta3-transfected alpha(v)beta3 expressing counterparts, xenografts derived from these cell lines, and fresh human cutaneous melanoma lesions comprising all stages of melanoma progression. Expression and activation status of matrix metalloproteinase-2 were studied by reverse transcription-polymerase chain reaction, immunohistochemistry, western blotting, and zymographic analysis, respectively. Matrix metalloproteinase-2 protein expression in vitro was similar in both alpha(v)beta3-negative and alpha(v)beta3-positive cell lines Remarkable differences, however, exist in the localization of inactive and active matrix metalloproteinase-2. Soluble active matrix metalloproteinase-2 was detectable only in the conditioned medium of alpha(v)beta3-negative cell lines and undetectable in the alpha(v)beta3-positive cell lines. Conversely, active matrix metalloproteinase-2 was present exclusively on the cell surface of the alpha(v)beta3 expressing transfectants. Western blot analysis of other components that are involved in matrix metalloproteinase-2 activation showed that processing of proMT1-matrix metalloproteinase to the activated form was enhanced in beta3 transfectants, whereas secretion of tissue inhibitor of metalloproteinase-2 was decreased. In vivo, the presence of functionally active matrix metalloproteinase-2 was significantly higher in xenografts derived from the alpha(v)beta3 expressing MV3 and BLM cell lines. In human cutaneous melanoma lesions, neither matrix metalloproteinase-2 nor integrin alpha(v)beta3 is detectable in melanoma in situ as determined by immunohistochemistry. In contrast, the number of matrix metalloproteinase-2-positive and alphavbeta3-positive tumor cells was clearly increased in primary melanomas, and melanoma metastases. Double staining experiments and confocal laser microscopy demonstrated that the percentage of cells coexpressing matrix metalloproteinase-2 and alpha(v)beta3 increased in advanced primary melanomas and melanoma metastases. In addition, zymography showed that functionally active matrix metalloproteinase-2 was frequently present in melanoma metastases. In these lesions a high proportion of matrix metalloproteinase-2- and alphavbeta3-double-positive melanoma cells were detectable. Our study demonstrates that the presence of activated matrix metalloproteinase-2 correlates with expression of alpha(v)beta3 in human melanoma cells both in vitro and in vivo, and also in fresh human melanoma lesions. These findings strongly suggest that co-ordinated expression of both factors may be required for melanoma cell invasion and metastasis formation.

Disease Progression↗
PubMed2004

A note on testing for homogeneity among effect sizes sharing a common control group.

L. V. Hedges and I. Olkin (1985) presented a statistic to test for homogeneity among correlated effect sizes and L. J. Gleser and I. Olkin (1994) presented a large-sample approximation to the covariance matrix of the correlated effect sizes. This article presents a more exact expression for this covariance matrix, assuming normally distributed data but not large samples, for the situation where effect sizes are correlated because a single control group was compared with more than one treatment group. After the correlation between effect sizes has been estimated, the standard Q statistic for correlated effect sizes can be used to test for homogeneity. This method is illustrated using results from schizophrenia research.

Humans↗
PubMed2006

Histological differences in new-onset IgA nephropathy between children and adults.

BACKGROUND: It is suggested that IgA nephropathy (IgAN) manifests differently in children vs adults on the basis of biopsy findings. However, this has been difficult to establish owing to the uncertainty of the timing of disease onset in adult IgAN. We addressed this question by comparing both histology and leucocyte accumulation in biopsies of recently diagnosed childhood and adult IgAN. METHODS: Biopsies taken within 2 years from the onset of renal abnormalities in 33 childhood (10 +/- 3 years of age) and 38 adult (35 +/- 6 years) cases of IgAN were examined for histological changes (cellularity in mesangial, endocapillary and extracapillary areas, matrix expansion, adhesions/crescents and interstitial damage), glomerular deposition of immunoglobulin and complement, and the presence of macrophages, activated macrophages and T cells by immunohistochemistry. RESULTS: Glomerular hypercellularity owing to increased cells in mesangial area was prominent in paediatric IgAN and significantly greater than in adult IgAN. In contrast, glomerular matrix expansion, crescent formation and interstitial damage were more severe in adults compared to paediatric IgAN. Indeed, glomerular hypercellularity correlated with proteinuria in paediatric but not in adult IgAN, whereas glomerular matrix correlated with proteinuria and renal function in adult but not in paediatric IgAN. The degree of C3c deposition was significantly greater in paediatric IgAN, while deposition of fibrinogen was greater in adult IgAN. Glomerular and interstitial CD68+ macrophages and a subset of sialoadhesin (Sn)+ activated macrophages were identified in both paediatric and adult IgAN, being significantly greater in number in adult IgAN. Glomerular leucocyte infiltration correlated with proteinuria while interstitial leucocyte infiltration correlated with interstitial damage in both groups. However, only the subset of Sn+ macrophages gave a significant correlation with renal function, glomerular hypercellularity and glomerular matrix. CONCLUSIONS: This study has demonstrated significant differences in the early glomerular lesions of IgAN in children vs adults. Furthermore, Sn+ activated macrophages are implicated in the pathogenesis of IgAN in both patient groups. The prognostic significance of these findings warrants further study.

Adolescent↗
PubMed2005

Suppressed TGF-beta1 expression is correlated with up-regulation of matrix metalloproteinase-13 in keloid regression after flashlamp pulsed-dye laser treatment.

BACKGROUND AND OBJECTIVES: Flashlamp pulsed-dye lasers (PDLs) has shown effectiveness in the treatment of keloids. In this study, we investigated whether PDL treatments decreased transforming growth factor-beta1 (TGF-beta1)-induction and up-regulation of matrix metalloproteinase (MMP) expression in keloid regression. STUDY DESIGN/MATERIALS AND METHODS: Keloid tissues obtained from 10 patients with intra-lesional or punch biopsies before and 7 days after PDL treatments [fluence per pulse was 10-18 J/cm2 (mean 14.0 J/cm2)]. Immunohistochemical (IHC) staining of TGF-beta1 and MMP-1 and MMP-13 expressions in keloid tissue was performed. Western blot analysis of MMP-1 and MMP-13 expressions in extracellular matrix was evaluated. RESULTS: IHC staining indicated that expression of TGF-beta1 was significantly reduced in keloid tissues after PDL irradiation. MMP-13 but not MMP-1 expression on IHC staining significantly increased in extracellular matrix of keloid tissues after PDL treatment. Western blot analysis also showed MMP-13 but not MMP-1 significant increased in keloid tissues after PDL treatment. CONCLUSIONS: Regression of keloids regressed after PDL treatments are associated with down-regulation of TGF-beta1 expression and up-regulation of MMP-13 activity.

Adolescent↗