Bleomycin and cyclophosphamide increase pulmonary type IV procollagen mRNA in mice

1990 ◽  
Vol 259 (2) ◽  
pp. L47-L52
Author(s):  
D. G. Hoyt ◽  
J. S. Lazo

Constant 7-day subcutaneous infusion of bleomycin (100 mg/kg) induces pulmonary fibrosis in C57Bl/6N mice, whereas BALB/cN mice are relatively resistant. In contrast, cyclophosphamide (200 mg/kg, ip) induces fibrosis in BALB/cN mice, whereas C57Bl/6N mice are resistant. The effect of these drugs on the pulmonary levels of mRNA encoding the major basement membrane components, laminin and type IV collagen, relative to poly (A+)RNA was determined in both C57Bl/6N and BALB/cN mice. In the sensitive C57Bl/6N mice, bleomycin increased alpha 1IV and alpha 2IV procollagen mRNA/poly (A+)RNA twofold in the absence of increases in laminin A, B1, and B2 mRNA/poly (A+)RNA. In the relatively resistant BALB/cN mice, bleomycin did not alter alpha 1IV procollagen mRNA/poly (A+)RNA and only transiently increased laminin A, B1, B2, and alpha 2IV procollagen mRNA/poly (A+)RNA. Similarly, cyclophosphamide increased alpha 1IV and alpha 2IV procollagen mRNA/poly (A+)RNA twofold in the sensitive BALB/cN mice and not in C57Bl/6N mice. Laminin mRNAs/poly (A+)RNA were not increased by cyclophosphamide in either strain. Thus, in these models, pulmonary fibrosis is preceded by a coordinate increase in steady-state levels of mRNA encoding basement membrane procollagen but is not associated with an increase in laminin gene expression

Development ◽  
1987 ◽  
Vol 99 (4) ◽  
pp. 509-519
Author(s):  
K.S. O'Shea

The distribution of basement membrane and extracellular matrix components laminin, fibronectin, type IV collagen and heparan sulphate proteoglycan was examined during posterior neuropore closure and secondary neurulation in the mouse embryo. During posterior neuropore closure, these components were densely deposited in basement membranes of neuroepithelium, blood vessels, gut and notochord; although deposition was sparse in the midline of the regressing primitive streak. During secondary neurulation, mesenchymal cells formed an initial aggregate near the dorsal surface, which canalized and merged with the anterior neuroepithelium. With aggregation, fibronectin and heparan sulphate proteoglycan were first detected at the base of a 3- to 4-layer zone of radially organized cells. With formation of a lumen within the aggregate, laminin and type IV collagen were also deposited in the forming basement membrane. During both posterior neuropore closure and secondary neurulation, fibronectin and heparan sulphate proteoglycan were associated with the most caudal portion of the neuroepithelium, the region where newly formed epithelium merges with the consolidated neuroepithelium. In regions of neural crest migration, the deposition of basement membrane components was altered, lacking laminin and type IV collagen, with increased deposition of fibronectin and heparan sulphate proteoglycan.


1993 ◽  
Vol 79 (6) ◽  
pp. 427-432 ◽  
Author(s):  
Marcello Guarino

Aims To investigate the distribution of basement membrane components type IV collagen and laminin in synovial sarcomas. Methods Paraffin sections from four synovial sarcomas were studied by the peroxidase-antiperoxldase procedure using specific antibodies to type IV collagen and laminin. Results Type IV collagen and laminin immunoreactivity was confined around epithelial areas in biphasic tumors. Several interruptions and discontinuities of the linear basement membrane profile were seen in sites of transition between mesenchymal and epithelial tissue. Moreover, a spot-like immunoreactivity was often observed in the spindle cell component of biphasic tumors. Monophasic tumors were either negative or showed a pericellular staining for both type IV collagen and laminin. Conclusions The distribution of basement membrane components is clearly related to the formation of epithelial elements in biphasic synovial sarcoma. The spot-like immunoreactivity of the spindle cell component, and the basement membrane interruptions at the boundary between mesenchymal and epithelial tissue, are both consistent with early basement membrane formation by developing epithelium. These findings support the concept that synovial sarcomas are basically soft tissue carcinosarcomas and that the epithelial component of the tumors develops by conversion of mesenchyme to epithelium.


1983 ◽  
Vol 31 (1A_suppl) ◽  
pp. 159-163 ◽  
Author(s):  
G.W. Laurie ◽  
C.P. Leblond

Immunohistochemistry was used to identify basement membrane components and examine their production by associated cells. Four substances were identified in a series of basement membranes in rats aged 20 days to 34 months, namely, type IV collagen, laminin, heparan sulfate proteoglycan, and fibronectin. They were then all localized to the basal lamina part of basement membranes and, presumably, are integrated within this layer. The production of type IV collagen was first examined in the embryonic endodermal cells associated with Reichert's membrane in the rat parietal yolk sac. The rough endoplasmic reticulum (rER), Golgi apparatus, and putative secretory granules of endodermal cells were immunostained, suggesting that these organelles participated in the biogenesis of type IV collagen. However, in rats aged 20 days or more, the cells associated with basement membranes were usually unstained. An exception was noted in the continually growing incisor tooth where the endothelial cells at the proliferating end usually showed immunostaining of rER and Golgi apparatus. It is, therefore, proposed that the formation of type IV collagen for basement membrane occurs at an early stage of development in the life of producer cells. Little is known of the formation of other basement membrane components during development, but there is immunohistochemical evidence that laminin and fibronectin are produced along the same secretory pathway as type IV collagen.


1992 ◽  
Vol 262 (1) ◽  
pp. F131-F137 ◽  
Author(s):  
Y. Natori ◽  
Y. M. O'Meara ◽  
E. C. Manning ◽  
A. W. Minto ◽  
J. S. Levine ◽  
...  

To study the formation of basement membrane by glomerular epithelial cells (GECs), production and secretion of type IV collagen and laminin by rat GECs in culture were evaluated. GECs produced two chains of type IV collagen (180 and 170 kDa) in the ratio of approximately 2 to 1, when immunoprecipitated with antibody to type IV collagen of mouse Engelbreth-Holm-Swarm (EHS) sarcoma. GECs also produced proteins that were precipitated by antibody to EHS laminin, i.e., two bands each in the positions of the A and B chains of mouse laminin. On enzyme-linked immunosorbent assay (ELISA), type IV collagen and laminin were found mainly in the cell-associated fraction and in the subepithelial culture medium. Confluent GECs on membrane filters formed a tight barrier against the flux of macromolecules. Under these conditions, 80% of newly synthesized and secreted matrix proteins were detected in the basolateral medium. Moreover, treatment with ammonium chloride, which is known to affect polarized secretion, caused both type IV collagen and laminin to be secreted via the basolateral and apical surfaces in similar amounts. These results indicate that cultured GECs are polarized and that they produce and secrete basement membrane components via the basolateral side.


Development ◽  
1988 ◽  
Vol 104 (1) ◽  
pp. 41-49 ◽  
Author(s):  
M. Solursh ◽  
K.L. Jensen

The study describes the distribution of several basement membrane molecules in the embryonic chick wing bud from stages 23 to 26, during the onset of myogenesis and chondrogenesis, and then later at stage 28. Laminin is localized as early as stage 23, prior to the onset of myogenesis, in regions corresponding to the position of the future dorsal and ventral myogenic areas. Other matrix components, including fibronectin, do not differentially accumulate in these same regions. Fibronectin, basement membrane heparan sulphate proteoglycan and type IV collagen are more widespread in their distribution than laminin, and are even present between mesenchymal cells. These results suggest a role for laminin in the initial differentiation of the muscle masses and emphasize that components of basement membrane can also be associated with mesenchymal cells.


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