Overexpression of pulmonary surfactant apoprotein A mRNA in alveolar type II cells and nonciliated bronchiolar (Clara) epithelial cells in streptozotocin-induced diabetic rats demonstrated by in situ hybridization.

Pulmonary surfactant is critical for gas exchange and is composed of both phospholipids and specific surfactant-associated proteins. The most abundant surfactant protein is termed surfactant apoprotein A (SP-A). This protein is thought to be important in the formation of tubular myelin, in absorption of surfactant to the air-liquid interface, in recycling of surfactant in alveolar type II cells, and in the regulation of secretion. We have examined the expression and localization of SP-A mRNA in streptozotocin-induced diabetic rats by in situ hybridization using a specific rat cDNA probe. Diabetes was induced by intraperitoneal injection of 60 mg/kg streptozotocin. After 10 wk, lungs were excised and examined by in situ hybridization and by light and electron microscopy. The ultrastructural examination demonstrated the marked changes of endoplasmic reticulum of alveolar type II cells, as reported previously. Immunohistostaining of SP-A in diabetic lungs was weak in alveolar type II cells. However, by autoradiographs of in situ hybridization, compared with the control lungs, a larger number of silver grains for the SP-A mRNA were shown in alveolar type II cells and also in some bronchiolar epithelial (Clara) cells from the diabetic lungs. Alveolar type II cells having high contents of silver grains were also increased in number. These results were confirmed by measurement of the SP-A content and by Northern blot analysis. The present study demonstrates an overexpression of SP-A mRNA despite the ultrastructural changes in the endoplasmic reticulum of alveolar type II cells in the diabetic lungs, which will provide new information on the regulatory mechanism of SP-A gene expression.(ABSTRACT TRUNCATED AT 250 WORDS)

[1]  G. Hook,et al.  Plasma proteins of the bronchoalveolar surface of the lungs of smokers and nonsmokers. , 2015, The American review of respiratory disease.

[2]  J. Wilson,et al.  Receptor-mediated gene delivery in vivo. Partial correction of genetic analbuminemia in Nagase rats. , 1991, The Journal of biological chemistry.

[3]  M. Perricaudet,et al.  Adenovirus-mediated transfer of a recombinant alpha 1-antitrypsin gene to the lung epithelium in vivo. , 1991, Science.

[4]  B. Olsen,et al.  Spatiotemporal pattern of type X collagen gene expression and collagen deposition in embryonic chick vertebrae undergoing endochondral ossification , 1991, The Anatomical record.

[5]  T. Hazinski,et al.  Localization and induced expression of fusion genes in the rat lung. , 1991, American journal of respiratory cell and molecular biology.

[6]  M. Matsuo,et al.  Effect of Dexamethasone on Pulmonary Surfactant Metabolism in Hyperoxia-Treated Rat Lungs , 1991, Pediatric Research.

[7]  R. Auten,et al.  Surfactant apoprotein A (SP-A) is synthesized in airway cells. , 1990, American journal of respiratory cell and molecular biology.

[8]  J. Minna,et al.  Mutations in the p53 gene are frequent in primary, resected non-small cell lung cancer. Lung Cancer Study Group. , 1990, Oncogene.

[9]  Matthew P. Anderson,et al.  Expression of cystic fibrosis transmembrane conductance regulator corrects defective chloride channel regulation in cystic fibrosis airway epithelial cells , 1990, Nature.

[10]  B. Vogelstein,et al.  Suppression of human colorectal carcinoma cell growth by wild-type p53. , 1990, Science.

[11]  A. Miller,et al.  Progress toward human gene therapy. , 1990, Blood.

[12]  K. Mechtler,et al.  Transferrin-polycation-mediated introduction of DNA into human leukemic cells: stimulation by agents that affect the survival of transfected DNA or modulate transferrin receptor levels. , 1990, Proceedings of the National Academy of Sciences of the United States of America.

[13]  M. Cotten,et al.  Transferrin-polycation conjugates as carriers for DNA uptake into cells. , 1990, Proceedings of the National Academy of Sciences of the United States of America.

[14]  B. Sanwal,et al.  Ethyl-3,4-dihydroxybenzoate inhibits myoblast differentiation: evidence for an essential role of collagen , 1990, The Journal of cell biology.

[15]  J. Minna,et al.  p53: a frequent target for genetic abnormalities in lung cancer. , 1989, Science.

[16]  M. Magnuson,et al.  Rapid CommunicationRapid Communication: In vivo Transfection of Murine Lungs with a Functioning Prokaryotic Gene using a Liposome Vehicle , 1989 .

[17]  L. Tsui,et al.  Identification of the cystic fibrosis gene: genetic analysis. , 1989, Science.

[18]  T. Friedmann,et al.  Progress toward human gene therapy. , 1989, Science.

[19]  R. Boucher,et al.  Intracellular Cl- activity and cellular Cl- pathways in cultured human airway epithelium. , 1989, The American journal of physiology.

[20]  C. Wu,et al.  Receptor-mediated gene delivery and expression in vivo. , 1988, The Journal of biological chemistry.

[21]  J. J. Batenburg,et al.  The pulmonary surfactant system: biochemical aspects and functional significance. , 1988, Physiological reviews.

[22]  D. Voelker,et al.  Pulmonary surfactant apoprotein A structure and modulation of surfactant secretion by rat alveolar type II cells. , 1988, The Journal of biological chemistry.

[23]  J. Northrop,et al.  Lipofection: a highly efficient, lipid-mediated DNA-transfection procedure. , 1987, Proceedings of the National Academy of Sciences of the United States of America.

[24]  K. Sano,et al.  Isolation and sequence of a cDNA clone for the rat pulmonary surfactant-associated protein (PSP-A). , 1987, Biochemical and biophysical research communications.

[25]  C H Wu,et al.  Receptor-mediated in vitro gene transformation by a soluble DNA carrier system. , 1987, The Journal of biological chemistry.

[26]  C. Finch,et al.  The physiology of transferrin and transferrin receptors. , 1987, Physiological reviews.

[27]  C. Mendelson,et al.  Insulin inhibits the accumulation of the major lung surfactant apoprotein in human fetal lung explants maintained in vitro. , 1987, Endocrinology.

[28]  M. Williams,et al.  Immunocytochemical localization of the major surfactant apoproteins in type II cells, Clara cells, and alveolar macrophages of rat lung. , 1986, The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society.

[29]  B. Olsen,et al.  Differential localization of mRNAs of collagen types I and II in chick fibroblasts, chondrocytes, and corneal cells by in situ hybridization using cDNA probes , 1986, The Journal of cell biology.

[30]  P. Farrell,et al.  Fetal Lung Development in the Diabetic Pregnancy , 1985, Pediatric Research.

[31]  K. Sugahara,et al.  Insulin binding and effects on glucose and transepithelial transport by alveolar type II cells. , 1984, The American journal of physiology.

[32]  W. Anderson,et al.  Prospects for human gene therapy. , 1984, The Journal of reproductive medicine.

[33]  M. Greaves,et al.  The transferrin receptor , 1982 .

[34]  A. van der Eb,et al.  A new technique for the assay of infectivity of human adenovirus 5 DNA. , 1973, Virology.

[35]  M. Cotten,et al.  Receptor-mediated transport of DNA into eukaryotic cells. , 1993, Methods in enzymology.

[36]  M. Watford,et al.  Effects of metabolic acidosis and diabetes on the abundance of specific renal mRNAs. , 1989, The International journal of biochemistry.

[37]  D. States,et al.  The alpha 1-antitrypsin gene and its mutations. Clinical consequences and strategies for therapy. , 1989, Chest.

[38]  Bjarne Andresen,et al.  Optimal staging of endoreversible heat engines , 1980 .