Biomedical subjects

Krzysztof Sobolewski

Publications and source records attributed to Krzysztof Sobolewski.

9 recordsLinked to original sources

PubMed2005

Evaluation of enzymes involved in proteoglycan degradation in the wall of abdominal aortic aneurysms.

The abdominal aortic aneurysm (AAA) wall represents an extreme example of arterial remodeling with disturbed elastin, collagen and proteoglycan metabolism. The aim of this study was to evaluate enzymes involved in the degradation of glycosaminoglycan chains and core proteins of proteoglycans in the AAA wall. The study material consisted of wall samples from 10 AAA. Fragments of 5 normal abdominal aortas from organ donors were used as a control. The activity of endoglycosidases, exoglycosidases and sulfatases was measured using colorimetric methods. To assess matrix metalloproteinases (MMPs), Western blot and zymography were performed. The activity of endoglycosidase degrading chondroitin-4-sulfate was lower in the AAA wall. Endoglycosidase degrading heparan sulfate and dermatan sulfate, arylosulfatase B, as well as all the exoglycosidases assessed demonstrated higher activities in the AAA wall. Furthermore, increased expression of MMP1, MMP2 and MMP9 was also shown in the AAA wall. Zymography revealed decreased activity of pro-MMP2 and presence of pro-MMP9 in the AAA wall compared to the wall of normal aorta. Extensive changes in the activity of glycosaminoglycan-degrading enzymes and MMPs may influence the organization of the extracellular matrix network and lead to previously demonstrated changes in the proteoglycan and glycosaminoglycan content in the AAA wall.

Aorta, Abdominal↗

PubMed2004

Matrix metalloproteinases of human leiomyoma in various stages of tumor growth.

The amounts and activities of matrix metalloproteinases (MMPs) were studied in human myometrium and uterine leiomyomas in various stages of growth. It was found that both myometrium and the investigated tumors contain collagenolytic enzymes. MMP-1, MMP-2, MMP-3 and MMP-9 were found. Gelatinase A (MMP-2) is the most abundant. In control myometrium only 10% of this enzyme exists in an active form, whereas in tumors, especially in large ones, the values reach 30%. It is suggested that the high activity of MMP-2 is responsible for remodelling of extracellular matrix in the growing tumors.

Adult↗

PubMed2004

Deregulation of collagen metabolism in human stomach cancer.

OBJECTIVE: The defects of collagen metabolism are responsible for the disorganization of extracellular matrix in stomach cancer. Collagen through interaction with integrin receptors regulates the cellular growth, differentiation, gene expression, prolidase and gelatinase activity and plays an important role in tumorigenesis and invasiveness. Although extracellular metalloproteinases initiate the breakdown of collagen in tissues, the final step of its degradation is mediated by prolidase. Therefore, we decided to compare the degradation of collagen in control tissues to gastric cancer tissues. METHODS: We investigated the collagen content (hydroxyproline assay), expressions of beta(1) integrin, prolidase and gelatinases A and B (Western immunoblot) as well activities of prolidase (colorimetric assay) and gelatinases (zymography) in stomach cancer tissue (n = 10). The results were compared with corresponding data obtained for control tissues (n = 10). RESULTS: No differences in the collagen content were found between the studied tissue samples. However, an increase in free proline pool, enhanced gelatinase expression and elevated gelatinolytic activity were found in the tumor tissue. These phenomena were accompanied by a significant elevation in prolidase activity and an increase in beta(1) integrin expression in stomach cancer, compared to control tissue. CONCLUSION: The data presented suggest an enhancement of collagen turnover in stomach cancer. It may be suggested that the increased degradation of collagen by gelatinase in cancer tissue is balanced by an increased biosynthesis of this protein.

Blotting, Western↗

PubMed2004

Decreased expression of the insulin-like growth factor-I-binding protein-1 (IGFBP-1) phosphoisoform in pre-eclamptic Wharton's jelly and its role in the regulation of collagen biosynthesis.

Insulin-like growth factor-I (IGF-I) is known as an important stimulator of collagen and glycosaminoglycans (GAGs) biosynthesis in tissues. IGF-I activity is under control of IGF-I-binding proteins (IGFBPs) with different IGF-I-binding affinity. IGFBP-1 is known as an inhibitor of IGF-dependent functions. Some IGFBPs (e.g., IGFBP-1) may undergo phosphorylation that dramatically increases IGFBP affinity for IGF. Wharton's jelly represents a reservoir of IGF-I and its binding proteins (BPs). Pre-eclampsia, the most common, pregnancy-associated pathological syndrome, contributes to a significant decrease in IGF-I and IGFBP-1 content in Wharton's jelly, although it does not affect collagen content in this tissue. In the present study we show that control Wharton's jelly contains phosphorylated forms of IGFBP-1 that are dramatically dephosphorylated during pre-eclampsia. A dramatic decrease in IGF-I binding to immunoprecipitated IGFBP-1 from pre-eclamptic Wharton's jelly compared to the control was observed. Western immunoblot analysis with anti-phosphothreonine antibodies for immunoprecipitated IGFBP-1 from control and pre-eclamptic Wharton's jelly revealed that both tissues contain phosphorylated forms of IGFBP-1. However, a distinct decrease in the expression of phosphorylated IGFBP-1 from pre-eclamptic Wharton's jelly was observed. The functional significance of the phenomenon was found in cultured fibroblasts treated with IGFBP isolated from Wharton's jelly extracts. A significant decrease in collagen biosynthesis was found in the cells treated with IGFBP of control Wharton's jelly, while in the presence of IGFBP from pre-eclamptic Wharton's jelly, the rate of collagen biosynthesis was similar to that in the control cells. The result was corroborated by data showing increase in expression of IGF-I receptor and phosphorylated MAP kinases (ERK1 and ERK2) in fibroblasts cultured in the presence of IGFBP from pre-eclamptic Wharton's jelly, compared to control. The data suggest that the decrease in phosphorylated IGFBP-1 in pre-eclamptic Wharton's jelly may decrease IGF-I-binding affinity for IGF and increase the bioavailability of IGF-I for receptor interaction. This mechanism may facilitate IGF-I-dependent stimulation of fibroblasts to produce extracellular matrix (ECM) components even at a low IGF-I tissue level. Therefore, IGFBP-1 phosphoisoforms in Wharton's jelly may play an important role in the regulation of IGF-I-dependent functions during pre-eclampsia.

Adult↗

PubMed2004

[Basic fibroblast growth factor in leiomyoma].

Fibroblast growth factor (FGF) is a potent stimulator of collagen and glycosaminoglycan biosynthesis and may play an important role in extracellular matrix (ECM) remodelling. Heparin sulphate was shown to be the major proteoglycan molecule in ECM of leiomyoma. It shows ability to bind some growth factors, including FGF. It was decided to evaluate bFGF presence and binding in leiomyoma tissues. Our results show that bFGF binds to the leiomyoma components of different molecular mass. Most of bFGF was identified in large leiomyoma. We suggest that the level of bFGF in leiomyoma tissue may reflect the intensity of tumour growth.

Adult↗

PubMed2003

The activities of some glycosaminoglycan-degrading enzymes in uterine leiomyomas.

The activities of some glycosaminoglycan-degrading enzymes in uterine leiomyomas. Both normal human myometrium and uterine leiomyoma contain several glycosaminoglycans (GAGs). In contrast to many normal and tumour tissues the amount of hyaluronic acid (HA) is very low and the proportional amount of sulphated glycosaminoglycans is distinctly higher. We compared the activity of GAG-degrading enzymes in normal myometrium and in uterine leiomyomas. Growth of uterine leiomyomas results in significant reduction in the activities of neutral endoglycosidases degrading most of the sulphated glycosaminoglycans. The activities of acid endoglycosidases also decreased (with the exception of chondroitin-6-sulphate). Thus, the differentiated activity of glycosidases degrading glycosaminoglycans can be a factor modifying the quantity of GAGs.

Adult↗

PubMed2003

[Extracellular matrix of the umbilical cord vein in EPH gestosis and fibroblast growth factor].

It was found in our previous studies that EPH gestosis is accompanied by an extensive remodeling of the extracellular matrix of the umbilical cord. Studies were performed on the umbilical cord veins of 10 control and 10 newborns delivered by mothers with EPH gestosis. It was decided to determine umbilical cord vein ability to bind of labeled (125J)-basic fibroblast growth factor (bFGF), and FGF content by Western immunoblot and ELISA methods. Our experiments indicated that the extracts of umbilical cord vein contain endogenous bFGF and several soluble FGF-binding compounds of different molecular weight. It is of interest that EPH gestosis is associated with a decrease in bFGF content. It seems be possible that the decrease of bFGF amount may be one of the factors, which constrain the biosynthesis of collagen in EPH gestosis umbilical cord vein wall.

Blotting, Western↗

PubMed2002

[Gelatinolitic and proteolytic activity of Wharton's jelly in EPH-gestosis (preeclampsia)].

EPH-gestosis is accompanied by an extensive remodeling of the extracellular matrix of Wharton's jelly. The gelatinolytic and proteolytic activities were measured. A decrease in gelatinolityc activity and an increase in proteolytic activity in EPH-gestosis were observed. The decrease in gelatinase activity in EPH-gestosis may be one of factors involved in extracellular matrix rebuilding of Wharton's jelly.

Female↗

PubMed2002

Binding of the basic fibroblast growth factor (bFGF) by soluble components of human umbilical cord.

Pre-eclampsia, the most common pregnancy associated syndrome, is connected with remodelling of extracellular matrix of the umbilical cord tissues. Since the fibroblast growth factor (FGF) is known to be a stimulator of collagen and glycosaminoglycan biosynthesis, one may expect that it plays an important role in such a remodelling. Studies performed on the umbilical cords of 10 control and 10 pre-eclamptic newborns demonstrated that both the umbilical cord arterial wall and Wharton's jelly contain FGF mainly in complexes with the components of different molecular mass. Pre-eclampsia is associated with a decrease of endogenous FGF-binding by soluble high molecular mass components of the umbilical cord. It is suggested that FGF released from these complexes may be actively bound by fibroblasts of the umbilical cord, stimulating them to produce collagen and sulphated glycosaminoglycans.

Binding, Competitive↗