Monolayer cultures of human epithelial and endothelial cells were used to study the association of latent transforming growth
factor-β1 (TGF-β1) to extracellular matrices and its release and ...activation during matrix degradation. Human umbilical vein
endothelial cells and embryonic lung fibroblasts produced relatively high levels of TGF-β1, its propeptide (β1-latency-associated
protein), and latent TGF-β-binding protein and incorporated latent TGF-β1 into their matrices as shown by immunoblotting.
Amnion epithelial cells produced lower levels of these proteins. Confluent cultures of epithelial cells were exposed to matrix-degrading
proteases and glycosidases. Mast cell chymase, leukocyte elastase, and plasmin efficiently released matrix-bound latent TGF-β1
complexes, while chondroitinase ABC and heparitinases were ineffective. The ability of the proteases to activate recombinant
latent TGF-β1 was tested using growth inhibition assays and a novel sodium deoxycholate-polyacrylamide gel electrophoresis
followed by immunoblotting. Sodium deoxycholate solubilized M r 25,000 TGF-β1 but did not dissociate high M r latent TGF-β1 complexes, allowing separation of these forms by polyacrylamide gel electrophoresis. Mast cell chymase and
leukocyte elastase did not activate latent TGF-β1, suggesting that its release from matrix and activation are controlled by
different mechanisms. The release of TGF-β from the matrix by leukocyte and mast cell enzymes may contribute to the accumulation
of connective tissue in inflammation.
PURPOSEPathological vascular differentiation in retinal vein occlusion (RVO)-related neovessel formation remains poorly characterized. The role of intraocular lymphatic-like differentiation or ...endothelial progenitor cell activity has not been studied in this disease. METHODSVitrectomy was performed in an eye with hemi-RVO; the neovessel membrane located at the optic nerve head was removed and subjected to immunohistochemistry. Characterization of the neovascular tissue was performed using hematoxylin and eosin, α-smooth muscle actin, and the pan-endothelial cell (EC) adhesion molecule CD31. The expression of lymphatic EC markers was studied by lymphatic vessel endothelial hyaluronan receptor 1 (LYVE-1), podoplanin (PDPN), and prospero-related homeobox protein 1 (Prox-1). Potential vascular stem/progenitor cells were identified by active cellular proliferation (Ki67) and expression of the stem cell marker CD117. RESULTSThe specimen contained blood vessels lined by ECs and surrounded by pericytes. Immunoreactivity for LYVE-1 and Prox-1 was detected, with Prox-1 being more widely expressed in the active Ki67-positive lumen-lining cells. PDPN expression was instead found in the cells residing in the extravascular tissue. Expression of the stem cell markers CD117 and Ki67 suggested vascular endothelial progenitor cell activity. CONCLUSIONSIntraocular lymphatic-like differentiation coupled with progenitor cell activation may be involved in the pathology of neovessel formation in ischemia-induced human hemi-RVO.
Segmental cystic kidney tumours in children Taskinen, Seppo; Lohi, Jouko; Kivisaari, Reetta ...
Scandinavian journal of urology and nephrology,
01/2009, Letnik:
43, Številka:
6
Journal Article
Abstract
Objective. Segmental cystic tumours in the kidney are extremely rare in children. This study reports our experience of those tumours. Material and methods. The operative database from 1993 ...to 2008 of the Hospital for Children and Adolescents, University of Helsinki, was evaluated for segmental cystic renal tumours without any solid component. Patient records, imaging studies and pathology specimens were reviewed. Results. Four cases (three girls and one boy) were found; all were less than 3 years old at the time of diagnosis. All patients underwent kidney-preserving surgery with resection of the cystic tumour. Two patients had neoplasias: one cystic nephroma and one cystic partially differentiated nephroblastoma. Both of these patients had associated or predisposing disease (type I cystic pleuropulmonary blastoma of the lung and mulibrey nanism, respectively). Two patients had a non-neoplastic tumour; localized cystic disease of the kidney and segmental adult type autosomal dominant polycystic kidney disease. Neoplastic cystic tumours had a fibrous capsule in preoperative magnetic resonance imaging and also in operation, unlike non-neoplastic lesions. Conclusions. Preoperative and perioperative diagnosis is difficult in cases of segmental cystic kidney tumours in a child. If a neoplastic tumour is suspected complete resection of the tumour is mandatory.
TGF-β1 is the prototype of the so called TGF-β growth factor family. The family consists of an increasing number of different polypeptide modulators of cell growth, differentiation and morphogenesis. ...Numerous ways to regulate the expression of the TGF-β genes have been identified. Their expression can be affected by autocrine and paracrine mechanisms, and also by some other growth factors. TGF-β:s are also subject to regulation by retinoids, steroid hormones and vitamin D. Active TGF-β regulates transcription, and there is an increasing list of genes that are affected by TGF-β. A characteristic feature in the biology of TGF-β:s is that they are usually secreted from cells in latent forms. TGF-β was originally isolated from the conditioned medium of sarcoma virus transformed cells. The purification involved acidification, which, on the basis of current understanding, activates latent forms. Platelets and placenta are rich sources of TGF-β. We have recently found that TGF-β is not just secreted from cultured cells but is deposited in a latent form to the pericellular space, namely to the extracellular matrix. The latent complex consists of the small latent complex (TGF-β and its propeptide) and a high molecular weight protease resistant binding protein, LTBP (latent TGF-β binding protein). Protease-mediated release from the matrix is supposedly an initial step in the activation of the molecule, which possibly occurs in a coordinate way at the cell surface. The association of latent TGF-β complexes with the pericellular matrices and their release by proteinases implicates that these events participate in a number of biological events where enhanced or focal proteolysis takes place, including cell invasion, tissue remodeling and wound healing.
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