Biosynthesis of sulfated extracellular matrices by alveolar type II cells increases with time in culture

1997 ◽  
Vol 273 (4) ◽  
pp. L840-L847 ◽  
Author(s):  
Philip L. Sannes ◽  
Jody Khosla ◽  
Barry P. Peters
Keyword(s):  
Extracellular Matrices ◽  
Alveolar Type ◽  
Type I ◽  
Type Ii Cells ◽  
Type Ii ◽  
Potential Mechanism ◽  
Alveolar Type Ii Cells ◽  
Prolonged Culture ◽  
Phenotypic Transition ◽  
I Cells

The aim of this study was to determine the extent to which sulfate incorporated into biosynthesized basement membrane (BM) components increased as isolated type II cells progress toward a more type I cell-like phenotype from 7 to 21 days in culture. Specific sulfate cytochemistry, using high iron diamine, showed that type I-like cells in 21-day cultures deposited a more highly sulfated extracellular matrix. Biosynthetic labeling experiments using [35S]cysteine or [35S]sulfate as precursors confirmed the increased capacity of 21-day type I-like cells to biosynthesize sulfated BM components compared with type II-like cells in 7-day cultures, including a novel sulfated laminin. These biochemical changes in sulfation of BM components coincide with the established phenotypic transition from type II to type I cells during prolonged culture. More importantly, the data suggest that regulation of sulfation constitutes a potential mechanism by which type I and type II cells alter their environment in such a manner as to stabilize phenotype and modulate responses to growth factors.

scholarly journals Mechanical stretch activates piezo1 in caveolae of alveolar type I cells to trigger ATP release and paracrine stimulation of surfactant secretion from alveolar type II cells

2020 ◽  
Vol 34 (9) ◽  
pp. 12785-12804 ◽  
Author(s):  
Kathrin Diem ◽  
Michael Fauler ◽  
Giorgio Fois ◽  
Andreas Hellmann ◽  
Natalie Winokurow ◽  
...  
Keyword(s):  
Atp Release ◽  
Mechanical Stretch ◽  
Alveolar Type ◽  
Type I ◽  
Type Ii Cells ◽  
Type Ii ◽  
Alveolar Type Ii Cells ◽  
Surfactant Secretion ◽  
I Cells ◽  
Stimulation Of

scholarly journals Transitional human alveolar type II epithelial cells suppress extracellular matrix and growth factor gene expression in lung fibroblasts

2019 ◽  
Vol 317 (2) ◽  
pp. L283-L294 ◽  
Author(s):  
Kelly A. Correll ◽  
Karen E. Edeen ◽  
Rachel L. Zemans ◽  
Elizabeth F. Redente ◽  
Karina A. Serban ◽  
...  
Keyword(s):  
Growth Factor ◽  
Epithelial Cells ◽  
Surfactant Protein ◽  
Lung Fibroblasts ◽  
Alveolar Type ◽  
Type I ◽  
Type Ii Cells ◽  
Type Ii ◽  
Alveolar Type Ii Cells ◽  
I Cells

Epithelial-fibroblast interactions are thought to be very important in the adult lung in response to injury, but the specifics of these interactions are not well defined. We developed coculture systems to define the interactions of adult human alveolar epithelial cells with lung fibroblasts. Alveolar type II cells cultured on floating collagen gels reduced the expression of type 1 collagen (COL1A1) and α-smooth muscle actin (ACTA2) in fibroblasts. They also reduced fibroblast expression of hepatocyte growth factor (HGF), fibroblast growth factor 7 (FGF7, KGF), and FGF10. When type II cells were cultured at an air-liquid interface to maintain high levels of surfactant protein expression, this inhibitory activity was lost. When type II cells were cultured on collagen-coated tissue culture wells to reduce surfactant protein expression further and increase the expression of some type I cell markers, the epithelial cells suppressed transforming growth factor-β (TGF-β)-stimulated ACTA2 and connective tissue growth factor (CTGF) expression in lung fibroblasts. Our results suggest that transitional alveolar type II cells and likely type I cells but not fully differentiated type II cells inhibit matrix and growth factor expression in fibroblasts. These cells express markers of both type II cells and type I cells. This is probably a normal homeostatic mechanism to inhibit the fibrotic response in the resolution phase of wound healing. Defining how transitional type II cells convert activated fibroblasts into a quiescent state and inhibit the effects of TGF-β may provide another approach to limiting the development of fibrosis after alveolar injury.

Sulfation of extracellular matrices modifies responses of alveolar type II cells to fibroblast growth factors

1996 ◽  
Vol 271 (5) ◽  
pp. L688-L697 ◽  
Author(s):  
P. L. Sannes ◽  
J. Khosla ◽  
P. W. Cheng
Keyword(s):  
Growth Factors ◽  
Biological Significance ◽  
Alveolar Type ◽  
Type I ◽  
Type Ii Cells ◽  
Type Ii ◽  
Fibroblast Growth ◽  
Alveolar Type Ii Cells ◽  
Proliferation And Differentiation ◽  
Type Ii Cell

The pulmonary alveolar basement membrane (BM) associated with alveolar type II cells has been shown to be significantly less sulfated than that of type I cells. To examine the biological significance of this observation, we measured the incorporation of 5-bromodeoxyuridine (BrdU) as an indicator of DNA synthesis in isolated rat type II cells cultured for 72-120 h on substrata that were naturally sulfated, not sulfated, or chemically desulfated in serum-free, hormonally defined media, with and without selected growth factors. The percentage of cells incorporating BrdU was significantly elevated by desulfated chondroitin sulfate in the presence of fibroblast growth factor-2 (FGF-2 or basic FGF) and depressed by heparin in the presence of either FGF-1 or acidic FGF or FGF-2. This depressive effect was lost by removing sulfate from the heparin. Some responses were dependent on the period of time in culture and concentration and molecular weight of the substrata. These observations support the notion that sulfation per se of certain components of BM is a key determinant of type II cell responses to select growth factors that may define patterns of proliferation and differentiation.

Effects of oligohydramnios on lung growth and maturation in the fetal rat

2002 ◽  
Vol 282 (3) ◽  
pp. L431-L439 ◽  
Author(s):  
Joseph A. Kitterman ◽  
Cheryl J. Chapin ◽  
Jeff N. Vanderbilt ◽  
Nicolas F. M. Porta ◽  
Louis M. Scavo ◽  
...  
Keyword(s):  
Fetal Lung ◽  
Alveolar Type ◽  
Type I ◽  
Type Ii Cells ◽  
Type Ii ◽  
Lung Growth ◽  
Type I Cells ◽  
Fetal Lung Development ◽  
Fetal Rat ◽  
I Cells

Oligohydramnios (OH) retards fetal lung growth by producing less lung distension than normal. To examine effects of decreased distension on fetal lung development, we produced OH in rats by puncture of uterus and fetal membranes at 16 days of gestation; fetuses were delivered at 21 or 22 days of gestation. Controls were position-matched littermates in the opposite uterine horn. OH lungs had lower weights and less DNA, protein, and water, but no differences in saturated phosphatidylcholine, surfactant proteins (SP)-A and -B, and mRNA for SP-A, -B, -C, and -D. To evaluate effects on epithelial differentiation, we used RTI40 and RTII70, proteins specific in lung to luminal surfaces of alveolar type I and II cells, respectively. At 22 days of gestation, OH lungs had less RTI40 mRNA ( P < 0.05) and protein ( P < 0.001), but RTII70 did not differ from controls. With OH, type I cells (in proportion to type II cells) covered less distal air space perimeter ( P < 0.01). We conclude that OH, which retards lung growth, has little effect on surfactant and impedes formation of type I cells relative to type II cells.

scholarly journals UTP regulation of ion transport in alveolar epithelial cells involves distinct mechanisms

2009 ◽  
Vol 297 (3) ◽  
pp. L439-L454 ◽  
Author(s):  
Chuanxiu Yang ◽  
Lijing Su ◽  
Yang Wang ◽  
Lin Liu
Keyword(s):  
Ion Transport ◽  
Short Circuit ◽  
Alveolar Epithelial Cells ◽  
Alveolar Type ◽  
Channel Blockers ◽  
Type I ◽  
Type Ii Cells ◽  
Type Ii ◽  
Type I Cells ◽  
I Cells

UTP is known to regulate alveolar fluid clearance. However, the relative contribution of alveolar type I cells and type II cells to this process is unknown. In this study, we investigated the effects of UTP on ion transport in type I-like cell (AEC I) and type II-like cell (AEC II) monolayers. Luminal treatment of cell monolayers with UTP increased short-circuit current ( Isc) of AEC II but decreased Isc of AEC I. The Cl− channel blockers NPPB and DIDS inhibited the UTP-induced changes in Isc (Δ Isc) in both types of cells. Amiloride, an inhibitor of epithelial Na+ channels (ENaC), abolished the UTP-induced Δ Isc in AEC I, but not in AEC II. The general blocker of K+ channels, BaCl2, eliminated the UTP-induced Δ Isc in AEC II, but not in AEC I. The intermediate conductance (IKCa) blocker, clofilium, also blocked the UTP effect in AEC II. The signal transduction pathways mediated by UTP were the same in AEC I and AEC II. Furthermore, UTP increased Cl− secretion in AEC II and Cl− absorption in AEC I. Our results suggest that UTP induces opposite changes in Isc in AEC I and AEC II, likely due to the reversed Cl− flux and different contributions of ENaC and IKCa. Our results further imply a new concept that type II cells contribute to UTP-induced fluid secretion and type I cells contribute to UTP-induced fluid absorption in alveoli.

Modulation of bioelectric properties across alveolar type II cells by substratum

1989 ◽  
Vol 257 (4) ◽  
pp. C678-C688 ◽  
Author(s):  
G. R. Cott
Keyword(s):  
Cell Morphology ◽  
Short Circuit ◽  
Alveolar Type ◽  
Type I ◽  
Type Ii Cells ◽  
Type Ii ◽  
Alveolar Type Ii Cells ◽  
Capacitance Effects ◽  
Short Circuit Currents ◽  
Cells Cultured

Rat alveolar type II cells were cultured on collagen-coated filters (CCF) and human amnionic basement membrane (ABM) to determine the effect of culture substratum on the development of monolayer bioelectric properties. Monolayers cultured on both substrata rapidly developed bioelectric properties with similar time courses, monolayer capacitance values (approximately 1 muF/cm2), current-voltage relationships, and responses to stimulants and inhibitors of active ion transport. Increasing seeding densities tended to increase monolayer bioelectric properties regardless of culture substratum. Monolayers cultured on ABM had higher resistance values (491 vs. 291 omega.cm2) and lower short-circuit currents (2.85 vs. 4.51 muA/cm2) than monolayers with similar cell densities cultured on CCF. These differences in monolayer bioelectric properties were not due to differences in substratum resistance or capacitance effects. The relationships between monolayer bioelectric properties were also affected by the culture substratum. In additional experiments, cells cultured on contracted gels formed monolayers with high short-circuit currents (9.25 muA/cm2). Cell morphology varied depending on the culture substratum, with cells cultured on contracted gels appearing the most cuboidal, whereas the flattest and most attenuated cells were those cultured on ABM. On the basis of these observations, we conclude that culture substratum significantly affects the development of bioelectric properties across alveolar type II cell monolayers. In vivo the bioelectric properties across the alveolar epithelium may also vary with changes in cellular substratum or cell density (e.g., after acute lung injury) and possibly with cell morphology (e.g., alveolar type I vs. alveolar type II cells).

Expression of fibronectin mRNA splice variants by rabbit lung in vivo and by alveolar type II cells in vitro

1996 ◽  
Vol 271 (6) ◽  
pp. L972-L980
Author(s):  
W. M. Maniscalco ◽  
R. H. Watkins ◽  
M. H. Campbell
Keyword(s):  
Gene Transcription ◽  
Splice Variant ◽  
Splice Variants ◽  
Alveolar Type ◽  
Type I ◽  
Type Ii Cells ◽  
Type Ii ◽  
Alveolar Type Ii Cells ◽  
Injured Lung

Fibronectin (FN) is a multidomain glycoprotein with putative functions in tissue development and repair. In repair of alveolar injury, FN may promote the transition of type II epithelial cells to type I epithelial cells. Alternative splicing of FN mRNA, including the EIIIA and EIIIB exons, results in protein isoforms that have cell, tissue, and developmental specificity. The present work found that FN mRNA with the EIIIA exon was in fetal, adult, and oxidant-injured lung. The EIIIB splice variant, however, was restricted to fetal lung and adult lung recovering from oxidant injury. Because alveolar type II cells in vitro express FN, we examined the splice variants in two conditions that induce FN [transforming growth factor-beta 1 (TGF-beta 1) treatment and time in culture]. TGF-beta 1 increased both EIIIA and EIIIB mRNA abundance by 10-fold. Increased EIIIA isoform immunostaining was also noted. Type II cells that spontaneously express FN at 72 h in vitro had increased EIIIA and EIIIB mRNA and increased immunostaining for EIIIA. Nuclear runoff showed induction of FN gene transcription at 72 h in vitro. Together, these data show differential FN splice variant expression in lung, with EIIIB mRNA restricted to fetal and recovering oxidant-injured lung. Furthermore, the transition of type II cells to a type I-like cell is accompanied by increased FN gene transcription and induction of both EIIIA and EIIIB mRNA.

scholarly journals CD44high alveolar type II cells show stem cell properties during steady-state alveolar homeostasis

2017 ◽  
Vol 313 (1) ◽  
pp. L41-L51 ◽  
Author(s):  
Qian Chen ◽  
Varsha Suresh Kumar ◽  
Johanna Finn ◽  
Dianhua Jiang ◽  
Jiurong Liang ◽  
...  
Keyword(s):  
Alveolar Epithelium ◽  
Cell Subpopulation ◽  
Alveolar Type ◽  
Type I ◽  
Type Ii Cells ◽  
Type Ii ◽  
Cell Surface Molecule ◽  
Type I Cells ◽  
Blood Exchange ◽  
I Cells

The alveolar epithelium is composed of type I cells covering most of the gas-blood exchange surface and type II cells secreting surfactant that lowers surface tension of alveoli to prevent alveolar collapse. Here, we have identified a subgroup of type II cells expressing a higher level of cell surface molecule CD44 (CD44high type II cells) that composed ~3% of total type II cells in 5–10-wk-old mice. These cells were preferentially apposed to lung capillaries. They displayed a higher proliferation rate and augmented differentiation capacity into type I cells and the ability to form alveolar organoids compared with CD44low type II cells. Moreover, in aged mice, 18–24 mo old, the percentage of CD44high type II cells among all type II cells was increased, but these cells showed decreased progenitor properties. Thus CD44high type II cells likely represent a type II cell subpopulation important for constitutive regulation of alveolar homeostasis.

scholarly journals Lipoxin A4promotes lung epithelial repair whilst inhibiting fibroblast proliferation

2016 ◽  
Vol 2 (3) ◽  
pp. 00079-2015 ◽  
Author(s):  
Shengxing Zheng ◽  
Vijay K. D'Souza ◽  
Domokos Bartis ◽  
Rachel C.A. Dancer ◽  
Dhruv Parekh ◽  
...  
Keyword(s):  
Wound Repair ◽  
Alveolar Type ◽  
Type I ◽  
Type Ii Cells ◽  
Myofibroblast Differentiation ◽  
Type Ii ◽  
Fibroblast Proliferation ◽  
Alveolar Type Ii Cells ◽  
Collagen Production ◽  
Epithelial Repair

Therapy that promotes epithelial repair whilst protecting against fibroproliferation is critical for restoring lung function in acute and chronic respiratory diseases.Primary human alveolar type II cells were used to model the effects of lipoxin A4in vitroupon wound repair, proliferation, apoptosis and transdifferention. Effects of lipoxin A4upon primary human lung fibroblast proliferation, collagen production, and myofibroblast differentiation were also assessed.Lipoxin A4promoted type II cell wound repair and proliferation, blocked the negative effects of soluble Fas ligand/tumour necrosis factor α upon cell proliferation, viability and apoptosis, and augmented the epithelial cell proliferative response to bronchoaveolar lavage fluid (BALF) from acute respiratory distress syndrome (ARDS). In contrast, Lipoxin A4reduced fibroblast proliferation, collagen production and myofibroblast differentiation induced by transforming growth factor β and BALF from ARDS. The effects of Lipoxin A4were phosphatidylinositol 3′-kinase dependent and mediatedviathe lipoxin A4receptor.Lipoxin A4appears to promote alveolar epithelial repair by stimulating epitheial cell wound repair, proliferation, reducing apoptosis and promoting trans-differentiation of alveolar type II cells into type I cells. Lipoxin A4reduces fibroblast proliferation, collagen production and myofibroblast differentiation. These data suggest that targeting lipoxin actions may be a therapeutic strategy for treating the resolution phase of ARDS.

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