Expression Of Interstitial Collagenase Research Articles

Protective effect of MAAs extracted from Porphyra tenera against UV irradiation-induced photoaging in mouse skin

The objective of this study was to investigate the effect of Mycosporine-like amino acids (MAAs) extracted from Porphyra tenera skin against UV irradiation-induced photoaging using an ICR mouse model of skin photoaging and to explore the curative effects of the compounds in MAAs. The skin damage and collagenous tissue impairments induced by ultraviolet radiation were observed by histopathological analysis, and the effects of MAAs on protecting against skin damage and maintaining an intact structure of collagenous tissue were studied. The expression of NF-κB and the MAPK signaling pathway and nuclear transcription factors MMP-1, MMP-3 and TNF-α was analyzed used quantitative real-time reverse transcription-polymerase chain reaction (qRT-PCR) and ELISA assays. The results showed that the MAAs extracted from Porphyra tenera contained Porphyra-334 and shinorine, which could prevent skin photoaging induced by ultraviolet irradiation and reduce the damage to collagen and elastin. Meanwhile, MAAs significantly inhibited the decrease in hydroxyproline and collagen content and protected against pathological damage to collagen fibers in photoaging skin. MAAs resulted in a reduction in the expression of interstitial collagenase (MMP-1), matrix metalloproteinases (MMP-3) and tumor necrosis factor-α (TNF-α) and a reduction in the content of tissue matrix metalloproteinase (MMPs). Furthermore, MAAs may promote procollagen synthesis by downregulating the expression of TNF-α and downregulating the levels of MMPs, which demonstrates that MAAs are involved in matrix collagen synthesis by activating the NF-kB pathway in photoaging skin. Based on these results, we concluded that MAAs protect skin from UV irradiation-induced photodamage, and therefore, MAAs may be a potentially effective agent for the prevention of photoaging.

Protective effect of gelatin peptides from pacific cod skin against photoaging by inhibiting the expression of MMPs via MAPK signaling pathway

Chronic exposure to ultraviolet (UV) irradiation causes skin photoaging. This study was undertaken to identify the anti-photoaging mechanisms of gelatin hydrolysate (CH) derived from pacific cod skin. Quantitative real-time reverse transcription-polymerase chain reaction (qRT-PCR) and ELISA assays were used to investigate the effects of CH on matrix metalloproteinases (MMPs) and the signaling pathways after UV irradiation by using a mice skin photoaging model. The average molecular weight of CH was 1200Da, and 273/1000 residues were hydrophobic, Gly-Pro and Gly-Leu sequences and Arg at C-terminus appeared frequently in CH. CH improved pathological changes of collagen fibers and significantly inhibited collagen content reduction in photoaging skin. Moreover, CH blocked the up-regulated expression of interstitial collagenase (MMP-1), stromelysin 1 (MMP-3), and gelatinase (MMP-9) in photoaging skin. Besides, CH suppressed the activities of MMPs by increasing the contents of tissue inhibitors of matrix metalloproteinases (TIMPs). CH significantly reduced the UV irradiation-dependent up-regulated phosphorylation of ERK and p38 in the mitogen-activated protein kinase (MAPK) signaling pathway. Furthermore, it inhibited the activation of activator protein 1 (AP-1) by down-regulating the mRNA level of c-Jun and c-Fos, which are the two transcription factors responsible for the regulation of MMPs expression. CH can effectively protect against UV irradiation-induced skin photoaging by inhibiting the expression and the activity of MMPs.

Mycobacterium tuberculosis dysregulates MMP/TIMP balance to drive rapid cavitation and unrestrained bacterial proliferation.

Active tuberculosis (TB) often presents with advanced pulmonary disease, including irreversible lung damage and cavities. Cavitary pathology contributes to antibiotic failure, transmission, morbidity and mortality. Matrix metalloproteinases (MMPs), in particular MMP-1, are implicated in TB pathogenesis. We explored the mechanisms relating MMP/TIMP imbalance to cavity formation in a modified rabbit model of cavitary TB. Our model resulted in consistent progression of consolidation to human-like cavities (100% by day 28), with resultant bacillary burdens (>10(7) CFU/g) far greater than those found in matched granulomatous tissue (10(5) CFU/g). Using a novel, breath-hold computed tomography (CT) scanning and image analysis protocol, we showed that cavities developed rapidly from areas of densely consolidated tissue. Radiological change correlated with a decrease in functional lung tissue, as estimated by changes in lung density during controlled pulmonary expansion (R(2) = 0.6356, p < 0.0001). We demonstrated that the expression of interstitial collagenase (MMP-1) was specifically greater in cavitary compared to granulomatous lesions (p < 0.01), and that TIMP-3 significantly decreased at the cavity surface. Our findings demonstrated that an MMP-1/TIMP imbalance is associated with the progression of consolidated regions to cavities containing very high bacterial burdens. Our model provided mechanistic insight, correlating with human disease at the pathological, microbiological and molecular levels. It also provided a strategy to investigate therapeutics in the context of complex TB pathology. We used these findings to predict a MMP/TIMP balance in active TB and confirmed this in human plasma, revealing the potential of MMP/TIMP levels as key components of a diagnostic matrix aimed at distinguishing active from latent TB (PPV = 92.9%, 95% CI 66.1-99.8%, NPV = 85.6%; 95% CI 77.0-91.9%).

Interstitial collagenase, gelatinases A and B and their endogenous inhibitors in squamous cell cervical carcinomas

Interstitial collagenase and gelatinases are matrix metalloproteinases (MMP), which play the key role in tumor invasion and metastasis. The aim of this study was to elucidate the peculiarities of expression of interstitial collagenase (MMP-1), gelatinases A and B (MMP-2 and MMP-9) and their endogenous tissue inhibitors TIMP-1 and TIMP-2 as invasive factors of squamous cell carcinomas (SCC) of human cervical cancer. The study was carried out using 24 specimens of SCC and 11 specimens of adjacent to tumor morphologically normal tissue. All carcinoma specimens expressed E7 HPV-16 gene. It was shown that the increase of MMP-1 and MMP-9 expression and low of TIMP-1 and TIMP-2 expression makes the main contribution to the destructive (invasive) potential of SCC. The change of MMP-2 expression is not so significant and it is less influenced to the destructive potential. Moreover, substantial expression of MMP-1, MMP-2 and MMP-9 was registered in the specimens of morphologically normal adjoining to tumor tissue. This expression was found to make an additional contribution to the destructive potential of cervical tumor.

Expression of interstitial collagenase and its endogenous regulators in immortalized and transformed by HPV-16 E7 gene fibroblasts

Matrix metalloproteinases (MMPs) play a critical role in tumor development and invasion. The aim of this study is to elucidate peculiarity of expression of interstitial collagenase (MMP-1) and its endogenous regulators in the process of oncogenic transformation of fibroblasts by E7 gene of HPV16. Papilloma virus type 16 and 18 are aetiological factor of cervical cancer. We have studied expression of MTI-MMP, MMP-1, tissue inhibitor of these proteases TIMP-1 and urokinase-typeplasminogen activator (uAP). The study was carried out using fibroblasts immortalized by LT gene (IF) and transformed by E7 gene of HPV-16 fibroblasts (TF). Primary culture of Fisher rat embryo fibroblasts was used as a control (PF). mRNA expression was studied by RT-PCR, enzymatic activity--by hydrolysis of fluorogenic type I collagen. It was found that cell transformation is accompanied by: a) 2-3 fold induction of MT1-MMP mRNA expression (vs PF); b) the decrease in mRNA level of TIMP-1 (1,5-2 fold); c) unchanged uPA expression. Cell immortalization is accompanied by: a) the increase of MT1-MMP expression (1,5-2 fold); b) unchanged TIMP-1 expression; c) the increase of uPA expression (2-4 fold) (vs PF and TF). MMP secreted activity and activity in lysates of TF increased but the level of free endogenous MMP inhibitors decreased (vs IF). Data on gene expression are consistent with enzymatic data on the collagenolytic activity. These results suggest changes in enzyme/inhibitor/activator ratio both TF and IF and significant enhancement of the destructive potential of the TF.

Increased activation of nuclear factor-kappa B (NF-κB) in isolated peritoneal macrophages of patients with endometriosis

Endometriosis is characterized by pelvic inflammation that shows an increased number of activated peritoneal macrophages and their secreted products such as cytokines, growth factors, and angiogenic factors. Our results show that activation of nuclear factor-kappa B (NF-kappaB), a pro-inflammatory transcription factor, is statistically significantly increased in peritoneal macrophages from patients with endometriosis when compared with controls.

Expression of MMPs and TIMPs in liver fibrosis – a systematic review with special emphasis on anti-fibrotic strategies

In liver tissue matrix metalloproteinases (MMPs) and their specific inhibitors (tissue inhibitors of metalloproteinases, TIMPs) play a pivotal role in both, fibrogenesis and fibrolysis. The current knowledge of the pathophysiology of liver fibrogenesis with special emphasis on MMPs and TIMPs is presented. A systematic literature search was conducted. All experimental models of liver fibrosis that evaluated a defined anti-fibrotic intervention in vivo or in vitro considering MMPs and TIMPs were selected. The methodological quality of all these publications has been critically appraised using an objective scoring system and the content has been summarized in a table.

Modulation of Collagen and MMP-1 Gene Expression in Fibroblasts by the Immunosuppressive Drug Rapamycin: A DIRECT ROLE AS AN ANTIFIBROTIC AGENT?

We have examined whether rapamycin, an immunosuppressive drug, may exert part of its antifibrotic activity by directly targeting fibroblast extracellular matrix deposition. Incubation of human lung fibroblast (WI-26) cultures with rapamycin led to dose- and time-dependent reduction in the expression of types I and III collagens, both at the protein and mRNA levels. Rapamycin had no effect on collagen promoter activity but accelerated mRNA decay, indicating post-transcriptional control of collagen gene expression. In contrast, rapamycin significantly enhanced the expression of interstitial collagenase (MMP-1) at the protein and mRNA levels and transcriptionally. We determined that rapamycin efficiently activates AP-1-driven transcription by rapidly inducing c-jun/AP-1 phosphorylation with activation of the c-Jun N-terminal kinase (JNK) cascade, resulting in enhanced binding of AP-1.DNA complex formation and AP-1-dependent gene transactivation. Conversely, the JNK inhibitor SP600125 inhibited rapamycin-induced MMP-1 gene transactivation and AP-1/DNA interactions. A c-jun antisense expression vector efficiently prevented rapamycin-induced MMP-1 gene transcription. Pharmacological inhibition of either ERK or p38 MAPK pathways was without effect on rapamycin-induced MMP-1 gene expression. It thus appears that rapamycin may exert direct antifibrotic activities independent from its immunosuppressive action.

Acute and chronic hypoxia as well as 7‐day recovery from chronic hypoxia affects the distribution of pulmonary mast cells and their MMP‐13 expression in rats

Chronic hypoxia results in pulmonary hypertension due to vasoconstriction and structural remodelling of peripheral lung blood vessels. We hypothesize that vascular remodelling is initiated in the walls of prealveolar pulmonary arteries by collagenolytic metalloproteinases (MMP) released from activated mast cells. Distribution of mast cells and their expression of interstitial collagenase, MMP-13, in lung conduit, small muscular, and prealveolar arteries was determined quantitatively in rats exposed for 4 and 20 days to hypoxia as well as after 7-day recovery from 20-day hypoxia (10% O2). Mast cells were identified using Toluidine Blue staining, and MMP-13 expression was detected using monoclonal antibody. After 4, but not after 20 days of hypoxia, a significant increase in the number of mast cells and their MMP-13 expression was found within walls of prealveolar arteries. In rats exposed for 20 days, MMP-13 positive mast cells accumulated within the walls of conduit arteries and subpleurally. In recovered rats, MMP-13 positive mast cells gathered at the prealveolar arterial level as well as in the walls of small muscular arteries; these mast cells stayed also in the conduit part of the pulmonary vasculature. These data support the hypothesis that perivascular pulmonary mast cells contribute to the vascular remodelling in hypoxic pulmonary hypertension in rats by releasing interstitial collagenase.

Spatial and Temporal Pattern of Expression of Interstitial Collagenase, Stromelysin/Transin, Gelatinase A, and TIMP-1 during Experimental Gastric Ulcer Healing

Background/Aim: Controlled proteolysis is a prerequisite for cell migration, angiogenesis, and matrix remodelling during gastric ulcer healing. We studied the temporal and spatial expression of three matrix metalloproteinases, gelatinase A (MMP-2), interstitial collagenase (MMP-13), stromelysin (MMP-3), and their major inhibitor, tissue inhibitor of metalloproteinases-1 (TIMP-1) during experimental gastric ulcer healing induced in rats by acetic acid injection. Methods: Gastric tissue specimens were hybridized with antisense ³⁵S-labelled RNA probes and the autoradiographic signal was analyzed by a computer aided image system. Gelatinase activity was analyzed by in situ and gel zymography. Results: During gastric ulcer healing, MMP-2, MMP-3, and MMP-13 RNA expression was increased in stromal cells of the gastric mucosa bordering the ulcer, suggesting a prevalent role of non-epithelial cells in pericellular proteolysis. Gelatinolytic activity was increased during ulcer healing and it was associated with extracellular matrix of the healing mucosa and newly formed vessels. In contrast to MMP-2 RNA, which was homogeneously distributed in all layers of the ulcer bed, MMP-3 and MMP-13 RNAs were confined to the upper layers of the granulation tissue. TIMP-1 RNA was detected in both epithelial and stromal cells of the gastric mucosa adjacent to the ulcer, as well as in the granulation tissue of the ulcer bed. Both MMP and TIMP-1 expression returned to basal levels during the late stages of tissue remodeling. Conclusion: Gastric ulcer repair is associated with a transient expression of specific metalloproteinases and their inhibitors in a distinct anatomical pattern pointing to complex cellular and cell/matrix interactions in the various layers of the healing mucosa.

Ultraviolet-B irradiation and matrix metalloproteinases: from induction via signaling to initial events.

Effects of sunlight have fascinated researchers for decades because nearly every living thing on earth is likely to be exposed to sunlight and the ultraviolet (UV) fraction of it. In addition to detrimental long-term effects such as immunosuppression and skin cancer, premature aging of the skin (photoaging) is a well-documented consequence of exposure to UVA and UVB. Photoaged skin is biochemically characterized by an overgrowth of abnormal elastic fibers in the dermis and by a dramatic decrease of distinct collagen types. Ultraviolet irradiation induces delayed UV-responsive genes, among them matrix metalloproteinases, which degrade macromolecules of the extracellular matrix, a hallmark in carcinogenesis and aging. We are interested in UVB-triggered initial events and in subsequent signaling resulting in enhanced expression of two major members of the matrix metalloproteinase family, the interstitial collagenase (MMP-1) and stromelysin-1 (MMP-3), in human dermal fibroblasts. Especially, these skin cells play a central role in connective tissue breakdown in photoaging and as stromal cells in tumor invasion and metastasis by means of their capability to produce matrix metalloproteinases. In this review, we will focus on UVB-triggered induction of matrix metalloproteinases, the so far identified components of the UVB-modulated signal transduction pathway(s), and the UVB irradiation-associated generation of reactive oxygen species (ROS). Finally, a potentially novel aspect in UVB irradiation-mediated expression of interstitial collagenase and stromelysin-1-namely, the involvement of reactive nitrogen species (RNS)-is discussed.

Effects of human neutrophil peptide-1 on the expression of interstitial collagenase and type I collagen in human dermal fibroblasts.

Human neutrophil peptide-1 (HNP-1), a defensin with antimicrobial properties, is also thought to promote wound healing. To elucidate the mechanism by which wound healing is facilitated by this factor, we investigated the effect of HNP-1 on the expression of interstitial collagenase (matrix metalloproteinase 1, MMP-1), collagen types I and III, and tissue inhibitor of metalloproteinase 1 (TIMP-1) by cultured fibroblasts by means of RT-PCR and ELISA. Our results showed that synthetic HNP-1 increased the expression of proalpha1(I) collagen mRNA and protein. In contrast, the expression of MMP-1 was decreased at both the mRNA and protein levels. Our observations suggest that HNP-1 may promote wound repair by enhancing extracellular matrix deposition and by controlling its degradation.

Myocardial fibrosis in transforming growth factor-beta(1) (TGF-beta(1)) transgenic mice is associated with inhibition of interstitial collagenase.

TGF-beta(1) mediates effects on fibroblast proliferation and collagen synthesis in the myocardium. The extracellular matrix remodeling depends on the fibrillar collagen degrading matrix metalloproteinases (MMPs) and their inhibitors (TIMPs). The in vivo effects of TGF-beta(1) on the MMP/TIMP system in TGF-beta(1) overexpressing transgenic mice were studied. Male Alb/TGF-beta(1)(cys(223,225)ser) transgenic mice (TG) and nontransgenic controls (C; 8 weeks) were examined. Protein expression of collagen type I, -III, interstitial collagenase (Int Coll), MMP-2, -9, TIMP-1, -2, -4 and TGF-beta(1) as well as enzyme activity (MMP-2, -9) were measured (Western blots, zymographic assays). mRNA expression of the interstitial collagenase and MMP-9 was studied with the Light-Cycler based real-time PCR. Overexpression of TGF-beta(1) resulted in a 10-fold increase in plasma and a seven-fold increase in myocardial TGF-beta(1) concentrations. Relative heart weights increased (mg g(-1): 7.8 +/- 0.4 vs. 4.8 +/- 0.6, n = 6; P < 0.01) in TG compared to C. Collagen type I and III increased in TG (1.9-fold and 1.7-fold) compared to controls. Interstitial collagenase protein activity (- 91%) and mRNA expression (-75%) in TG were reduced (P < 0.05-P < 0.001). Gelatinase (MMP-2, MMP-9) expression and activity were not significantly alterated. MMP-inhibitors were increased 2.5-fold (TIMP-1, -4) and 6-fold (TIMP-2) in TG. TGF-beta(1) produces myocardial fibrosis in vivo. This effect is not only produced by a stimulation of matrix protein formation: a complex regulation of MMP and TIMP interaction, namely decrease of expression and activity of interstitial collagenase and an enhanced inhibition by increased levels of TIMPs, are involved. These mechanisms are optional targets for therapeutic interventions in myocardial diseases.

Effect of Ramipril and Furosemide Treatment on Interstitial Remodeling in Post-Infarction Heart Failure Rat Hearts

Extracellular matrix (ECM) remodeling and increased matrix metalloproteinase (MMP) expression and activity have been observed to be relevant in the development of heart failure (HF). We examined the effects of ramipril alone or with furosemide on ECM in a heart failure model. HF was induced by occlusion of the left coronary artery in spontaneously hypertensive rats (SHR). Rats were assigned to placebo (n=9), ramipril 1 mg/kg/day (n=11), furosemide 2×2 mg/kg/day (n=7) or both (1 mg/kg/day+2×2 mg/kg/dayn =8). LV-function, collagen content, MMP/TIMP (tissue inhibitor of matrix metalloproteinases) protein- and mRNA-expression were examined in non-infarcted LV tissue. MMP-2/TIMP-4 ratio was increased in HF. Ramipril reduced MMP-2 expression (active form), collagen type I mRNA expression and content and increased TIMP-4 levels associated with decreased left ventricular end diastolic pressure (LVEDP), mortality rate and increased LV pressure (LVP). Combination therapy with furosemide is less efficient with regard to collagen content and MMP-2 (active form) reduction but did not worsen beneficial effects of ramipril on LV function and mortality rate. Furosemide alone had no effect on MMP-2 (active form) expression, collagen content, LV function and mortality rate. Prevention of LV dilatation by ramipril was associated with decreased gelatinolytic activity and increased MMP-inhibition in heart failure SHR. Furthermore, ramipril reduced fibrosis by enhanced interstitial collagenase expression. Furosemide did not show the beneficial effects of ramipril on ECM remodeling but did not worsen LV function. Positive effects of furosemide treatment alone on LV remodeling and function were not observed.

Gene expression of interstitial collagenase in both progressive and recovery phase of rat liver fibrosis induced by carbon tetrachloride

Background/Aims: Liver fibrosis is a dynamic state between matrix production and degradation. Since our report in 1974, many studies have examined collagenase and liver fibrosis, but not the identification of cells responsible for collagenase production in vivo. The aim of this study was to investigate the gene expression of interstitial collagenase in the progressive and recovery phases of experimental rat liver fibrosis by in situ hybridization.Methods: We examined the gene expression of interstitial collagenase (MMP-13) in the progressive and recovery phase of experimental rat liver fibrosis induced by chronic CCl4 intoxication by reverse transcription-polymerase chain reaction (RT-PCR) and in situ hybridization. In order to identify the cells expressing MMP-13 mRNA by in situ hybridization, immunohistochemistry was performed using serial sections.Results: In normal rat liver, a faint band for MMP-13 mRNA was observed by RT-PCR, but not by in situ hybridization. The livers of rats treated with CCl4 for 4 weeks showed fatty metamorphosis but no definite fibrosis. Positive signals for MMP-13 mRNA were observed in scattered mesenchymal cells, within lobules which seem to be stellate cells from immunohistochemical staining. Once the fibrosis became prominent, the faint band for MMP-13 mRNA was detected only by RT-PCR and very few signals, if any, by in situ hybridization. On the other hand, in the recovery phase of liver fibrosis, gene expression of MMP-13 was markedly enhanced. Strong positive cells by in situ hybridization were observed mainly at the interface between the resolving fibrous septa and the parenchyma. Overlapping both images of in situ hybridization and immunohistochemical staining with the help of a computer revealed that some positive cells, but not all cells, were stellate cells stained with α-smooth muscle actin antibody.Conclusions: MMP-13 participates in the degradation of newly-formed matrix in the recovery from rat liver fibrosis more than in the remodeling of extracellular matrix for the formation of fibrosis. Hepatic stellate cells play a crucial role in MMP-13 production in the recovery from fibrosis, though not all stellate cells were positive for MMP-13 mRNA. Further investigation into gene expression of MMP-13 in recovery will lead to new strategies for the treatment of liver cirrhosis.

Monocyte chemoattractant protein-1 enhances gene expression and synthesis of matrix metalloproteinase-1 in human fibroblasts by an autocrine IL-1 alpha loop.

Monocyte chemoattractant protein-1 (MCP-1), a member of the C-C chemokine superfamily, has recently been shown to be involved in the pathogenesis of tissue fibrosis. In vitro studies demonstrated that MCP-1 up-regulates type I collagen gene expression via endogenous production of TGF-beta in rat lung fibroblasts. We here show that recombinant human MCP-1 affects gene expression of interstitial collagenase (matrix metalloproteinase-1 (MMP-1)) in primary human skin fibroblasts and a stable fibroblast cell line. MMP-1 mRNA was induced by MCP-1 (10 ng/ml) as early as 6 h and reached a maximal expression at 24 h. MCP-1 also caused an increase of MMP-2 mRNA expression in both types of fibroblasts at 48 h. Interestingly, tissue inhibitor of metalloproteinase-1 (TIMP-1) mRNA was also up-regulated by MCP-1, and TIMP-1 mRNA expression peaked at 48 h in both types of fibroblasts. Immunoblot analysis demonstrated increased levels of MMP-1 and TIMP-1 protein in the culture supernatants of primary fibroblasts stimulated with MCP-1. In addition, MCP-1 strongly induced IL-1 alpha mRNA expression in dermal fibroblasts in parallel with the induction of MMP-1. Preincubation with IL-1 receptor antagonist almost completely abrogated the expression of MMP-1 mRNA, and partially inhibited MMP-1 synthesis induced by MCP-1. Transient transfection of primary skin fibroblasts with a MMP-1 promoter-reporter construct indicated a dose-dependent increase in promoter activity by MCP-1 stimulation. These data demonstrate that MCP-1 up-regulates MMP-1 mRNA expression and synthesis in human skin fibroblasts at a transcriptional level and provide evidence that this is mediated by an IL-1 alpha autocrine loop.

Effects of sodium hyaluronate on experimental osteoarthritis in rabbit knee joints.

The aim of this study was to examine the effects of intraarticular administration of hyaluronan (HA) on cartilage degradation. Using a partial menisectomy model of osteoarthritis (OA) in the rabbit knee, the authors investigated the catabolic and anabolic changes induced by intraarticular injection of HA. To analyze anabolic changes, the authors assessed cell proliferation by measuring [3H] thymidine uptake, and proteoglycan biosynthesis by noting [35S] sulfate incorporation. For catabolic changes, messenger ribonucleic acid (mRNA) expression of interstitial collagenase (MMP-1), stromelysin-1 (MMP-3), and tissue inhibitor of metalloproteinase-1 (TIMP-1) in cartilage and synovium were detected with reverse transcriptase polymerase chain reaction (RT-PCR). Of significance for blocking the development of early OA in chondrocytes was the finding that total proteoglycan synthesis in the HA treatment group was significantly higher than in the controls. At the mRNA level in cartilage and synovium, HA inhibited MMP-3 and TIMP-1 production in the same way in the HA treatment group, while not affecting MMP-1 production. Thus it can be concluded that HA affects cartilage catabolism and anabolism to prevent the progress of OA.

Expression of interstitial collagenase (MMP-1) in fibroblastic cells of morphea induced by UVA-1 phototherapy

Expression of interstitial collagenase (MMP-1) in fibroblastic cells of morphea induced by UVA-1 phototherapy

Effects of bath PUVA therapy on the expression of interstitial collagenase (MMP-1) in morphea

Effects of bath PUVA therapy on the expression of interstitial collagenase (MMP-1) in morphea

What Is the Role of Vascular Endothelial Growth Factor-Related Molecules in Tumor Angiogenesis?

Growth of solid tumors depends on angiogenesis, the process by which new blood vessels develop from the endothelium of a pre-existing vasculature. 1 Tumors promote angiogenesis by secreting growth factors that stimulate endothelial migration, proliferation, proteolytic activity, and capillary morphogenesis. 2 Newly formed blood vessels supply the tumor with nutrients and oxygen, dispose of its metabolic waste products, and generate paracrine stimuli, which further promote tumor cell proliferation and invasiveness. 1,3 Among the known angiogenic factors, vascular endothelial growth factor (VEGF) has emerged as a central regulator of the angiogenic process in physiological and pathological conditions. 4 This molecule was first named vascular permeability factor by Dvorak and co-workers because of its potent stimulatory effect on the permeability of the tumor microvasculature. 5 Ferrara et al 6 coined the term VEGF to describe a mitogenic factor that selectively stimulated endothelial cell proliferation and angiogenesis. The same molecule was independently discovered by others. 7,8 Connolly et al 9 reported that vascular permeability factor was mitogenic for endothelial cells and had the capacity to stimulate vascular proliferation. Sequence analysis of cDNAs demonstrated that vascular permeability factor and VEGF were the same molecule. 4 Recently, the VEGF family of growth factors has expanded with the addition of four new molecules: placenta growth factor (PlGF), VEGF-B, VEGF-C, and VEGF-D (Table 1) ▶ . 10-13 VEGF and VEGF-related molecules have homologous amino acid sequences including eight cysteine residues, which are also found in platelet-derived growth factors A and B, and bind to the same class of tyrosine kinase receptors. 4,8 In this issue of the American Journal of Pathology, Salven et al 14 report that VEGF-B and VEGF-C are expressed in a variety of human tumors. This commentary briefly reviews our knowledge of this field and critically evaluates the potential role of VEGF-related molecules in tumor angiogenesis and neoplastic progression. Table 1. VEGF and VEGF-Related Molecules