Different Susceptibilities of Fibulin‐1 and Fibulin‐2 to Cleavage by Matrix Metalloproteinases and Other Tissue Proteases

Sasaki, Takako; Mann, Karlheinz; Murphy, Gillian; Chu, Mon‐Li; Timpl, Rupert

doi:10.1111/j.1432-1033.1996.0427h.x

Cited by 54 publications

(39 citation statements)

References 41 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…29 Several reports have indicated that chymase could be involved in tissue degradation by activating procollagenase 30 or by directly degrading extracellular matrix proteins such as fibronectin and fibulin-2. 31 These direct actions of chymase are independent of its AIIFA. Because the main actions reported for Ang II are cell proliferation 1 and migration 2 but not tissue degradation, higher tissue Ang II formation is unlikely to be the mechanism for the development of aneurysmal lesions, which are characterized by thinning of the medial layer of the aorta.…”

Section: Discussionmentioning

confidence: 99%

Increased Chymase-Dependent Angiotensin II Formation in Human Atherosclerotic Aorta

et al. 1999

View full text Add to dashboard Cite

Abstract-Locally formed angiotensin II (Ang II) and mast cells may participate in the development of atherosclerosis.Chymase, which originates from mast cells, is the major Ang II-forming enzyme in the human heart and aorta in vitro.The aim of the present study was to investigate aortic Ang II-forming activity (AIIFA) and the histochemical localization of each Ang II-forming enzyme in the atheromatous human aorta. Specimens of normal (nϭ9), atherosclerotic (nϭ8), and aneurysmal (nϭ6) human aortas were obtained at autopsy or cardiovascular surgery from 23 subjects (16 men, 7 women). The total, angiotensin-converting enzyme (ACE)-dependent, and chymase-dependent AIIFAs in aortic specimens were determined. The histologic and cellular localization of chymase and ACE were determined by immunocytochemistry. Total AIIFA was significantly higher in atherosclerotic and aneurysmal lesions than in normal aortas. Most of AIIFA in the human aorta in vitro was chymase-dependent in both normal (82%) and atherosclerotic aortas (90%). Immunocytochemical staining of the corresponding aortic sections with antichymase, antitryptase or anti-ACE antibodies showed that chymase-positive mast cells were located in the tunica adventitia of normal and atheromatous aortas, whereas ACE-positive cells were localized in endothelial cells of normal aorta and in macrophages of atheromatous neointima. The density of chymase-and tryptase-positive mast cells in the atherosclerotic lesions was slightly but not significantly higher than that in the normal aortas, and the number of activated mast cells in the aneurysmal lesions (18%) was significantly higher than in atherosclerotic (5%) and normal (1%) aortas. Our results suggest that local Ang II formation is increased in atherosclerotic lesions and that chymase is primarily responsible for this increase. The histologic localization and potential roles of chymase in the development of atherosclerotic lesions appear to be different from those of ACE. (Hypertension. 1999;33:1399-1405.)

show abstract

Section: Discussionmentioning

confidence: 99%

Increased Chymase-Dependent Angiotensin II Formation in Human Atherosclerotic Aorta

et al. 1999

View full text Add to dashboard Cite

show abstract

“…Additionally, the 26 kDa fragment was only detectable in ERapositive breast carcinomas and ERa-positive breast cancer- approximately 26 kDa (Sasaki et al, 1996), which may correspond to the immunoreactive fragment observed in this study. Intriguingly, elastases are also elevated in breast cancer (Kao and Stern, 1986).…”

Section: Erα-negativementioning

confidence: 93%

“…Indeed, fibulin-1 proteolysis has already been described in vitro (Sasaki et al, 1996) and in studies of cultured skin fibroblastic cells (Debeer et al, 2002), as well as in the skin of mice exhibiting 2,4-dinitrofluorobenzene-induced chronic contact dermatitis (Kusubata et al, 1999). Other explanations for the origin of the N-terminal fibulin-1 fragments include differential alternative splicing and/or the usage of internal ribosome entry sites.…”

Section: Erα-negativementioning

confidence: 99%

Elevated expression and altered processing of fibulin-1 protein in human breast cancer

et al. 2003

View full text Add to dashboard Cite

The extracellular matrix protein fibulin-1 suppresses the motility and invasiveness of a variety of tumour cell types in vitro as well as the growth of fibrosarcoma tumours in nude mice. In this study, fibulin-1 protein expression in breast carcinoma specimens and normal breast tissue was evaluated immunohistologically. Fibulin-1 protein expression was also semiquantitatively assessed by immunoblot analysis in a collection of normal breast tissues (n ¼ 18), benign tumours (n ¼ 5) and breast carcinomas (n ¼ 39). In normal breast tissue, fibulin-1 protein expression predominated in the ductal epithelium and underlying myoepithelium, with weaker staining evident in the loose connective surrounding the ducts. Examination of breast carcinomas revealed that the tumour cells also expressed fibulin-1 protein. The level of mature fibulin-1 polypeptide (100 kDa) was higher in the breast carcinoma specimens as compared to normal breast tissue (Mann -Whitney U-test, P ¼ 0.0005). In addition to the mature fibulin-1 polypeptide, several smaller sized polypeptides of 55, 50 and 25 kDa were detected using monoclonal antibodies reactive towards an epitope located at the N-terminus of fibulin-1. The immunoreactive 50 kDa polypeptide was detected more frequently in breast carcinoma specimens than in normal breast tissue (w 2 ¼ 17.22, Po0.0001). Furthermore, the ratio of the 50 kDa fragment to the mature fibulin-1 polypeptide correlated with the level of oestrogen receptor a (Spearman correlation coefficient, rs ¼ 0.49, Po0.003, n ¼ 36) and progesterone receptor (rs ¼ 0.43, P ¼ 0.008, n ¼ 36) expression in the tumour specimens. Taken together, these findings indicate that elevated expression and altered processing of fibulin-1 is associated with human breast cancer.

show abstract

“…Poly(A) ϩ RNA was recovered from total RNA with an RNA Polytex-Kit (Qiagen Tissue extraction and protein analysis. Tissues from various organs were extracted following a previously established protocol (45). Protein extracts were used for immunoblotting and radioimmunoassays.…”

Section: Methodsmentioning

confidence: 99%

Gene Structure and Functional Analysis of the Mouse Nidogen-2 Gene: Nidogen-2 Is Not Essential for Basement Membrane Formation in Mice

Schymeinsky

Nedbal

Miosge

et al. 2002

Molecular and Cellular Biology

Self Cite

128

122

View full text Add to dashboard Cite

Nidogens are highly conserved proteins in vertebrates and invertebrates and are found in almost all basement membranes. According to the classical hypothesis of basement membrane organization, nidogens connect the laminin and collagen IV networks, so stabilizing the basement membrane, and integrate other proteins. In mammals two nidogen proteins, nidogen-1 and nidogen-2, have been discovered. Nidogen-2 is typically enriched in endothelial basement membranes, whereas nidogen-1 shows broader localization in most basement membranes. Surprisingly, analysis of nidogen-1 gene knockout mice presented evidence that nidogen-1 is not essential for basement membrane formation and may be compensated for by nidogen-2. In order to assess the structure and in vivo function of the nidogen-2 gene in mice, we cloned the gene and determined its structure and chromosomal location. Next we analyzed mice carrying an insertional mutation in the nidogen-2 gene that was generated by the secretory gene trap approach. Our molecular and biochemical characterization identified the mutation as a phenotypic null allele. Nidogen-2-deficient mice show no overt abnormalities and are fertile, and basement membranes appear normal by ultrastructural analysis and immunostaining. Nidogen-2 deficiency does not lead to hemorrhages in mice as one may have expected. Our results show that nidogen-2 is not essential for basement membrane formation or maintenance.

show abstract

Different Susceptibilities of Fibulin‐1 and Fibulin‐2 to Cleavage by Matrix Metalloproteinases and Other Tissue Proteases

Cited by 54 publications

References 41 publications

Increased Chymase-Dependent Angiotensin II Formation in Human Atherosclerotic Aorta

Increased Chymase-Dependent Angiotensin II Formation in Human Atherosclerotic Aorta

Elevated expression and altered processing of fibulin-1 protein in human breast cancer

Gene Structure and Functional Analysis of the Mouse Nidogen-2 Gene: Nidogen-2 Is Not Essential for Basement Membrane Formation in Mice

Contact Info

Product

Resources

About