PubMed Health⌕ Search

Biomedical subjects

I Caniggia

Publications and source records attributed to I Caniggia.

At least 19 recordsLinked to original sources
PubMed2002

TGF-beta 3 expression during umbilical cord development and its alteration in pre-eclampsia.

Members of the TGF-beta family have been shown to play an important role in numerous tissues during development. In the present study we have investigated the spatial and temporal expression of TGF-beta 3, in human umbilical cord development. Total TGF-beta 3 protein content, assessed by immunoblotting, increased with advancing gestation as did immunostaining and mRNA in Wharton's jelly fibroblasts. Immunohistochemical analysis revealed that TGF-beta 3 was present in all cell types. Temporal changes in TGF-beta 3 expression were observed in the vascular smooth muscle cells, such that with advancing gestation TGF-beta 3 protein expression and became mostly restricted to the extracellular compartment of the vascular media. This was associated with a decrease in TGF-beta 3 mRNA expression in umbilical vascular smooth muscle cells. Of clinical significance, umbilical cords from pregnancies complicated by pre-eclampsia, showed a significant reduction in total TGF-beta 3 protein expression when compared to those of age-matched patients. Both TGF-beta 3 mRNA and protein expression were downregulated in the endothelium and smooth muscle layers of the umbilical arteries, as well as in the Wharton jelly fibroblasts. Our data demonstrate that during umbilical cord development TGF-beta 3 expression is spatially and temporally regulated and that TGF-beta 3 expression is altered in umbilical cords of pregnancies complicated by pre-eclampsia. We speculate that the downregulation of TGF-beta 3 expression found in pre-eclamptic umbilical cord may contribute to the abnormal structure and mechanical properties seen in these pathological umbilical cords.

Case-Control Studies↗
PubMed2002

Mechanisms of oxygen sensing in human trophoblast cells.

During pregnancy, changes in oxygen tension are essential for proper embryonic and placental development. Little is known about the mechanisms underlying mammalian cellular adaptations to changes in oxygen tension. Currently, we have explored putative mechanisms by which human trophoblast cells may sense oxygen. In order to investigate a role for hemoproteins in oxygen sensing, we cultured human villous explants of 5-8 weeks gestation under 20 per cent O(2) in the presence of either cobalt chloride or desferrioxamine, which interfere with the ability of iron (heme) to interact with oxygen. Treatment with these compounds mimicked hypoxia by stimulating the low oxygen effect on extravillous trophoblast outgrowth (EVT) and inducing HIF-1alpha expression, analogous to that observed in explants cultured at 3 per cent O(2). Addition of unhindered iron, in the form of iron chloride, to the treated-explants reversed the stimulatory effect on EVT outgrowth and HIF-1alpha expression. Subsequently, in order to probe into a mitochondrial role in trophoblast oxygen sensing, we cultured first trimester villous explants under 3 per cent O(2) in the presence of either diphenyleneiodonium or rotenone, known inhibitors of flavin-containing proteins. Treated-explants showed inhibition of the typical low oxygen-induced EVT outgrowth, when compared to untreated controls. Thus, this data supports a hypothesis that trophoblast cells may utilize mitochondria and/or hemoproteins as oxygen sensors to detect the critical changes in oxygen tension during pregnancy.

Adult↗
PubMed2002

Adriana and Luisa Castellucci Award lecture 2001. Hypoxia inducible factor-1: oxygen regulation of trophoblast differentiation in normal and pre-eclamptic pregnancies--a review.

During early pregnancy, trophoblast differentiation occurs in an environment of relative low oxygen tension which is essential for normal embryonic and placental development. At around 10-12 weeks' gestation, when the intervillous space opens to maternal blood, there is an increase in Po(2). This increase correlates with the time of maximal trophoblast invasion into the maternal decidua, which allows extravillous trophoblast cells to access and remodel the maternal spiral arteries. Hypoxia Inducible Factor 1(HIF-1) is a transcription factor which activates gene transcription in response to varying oxygen concentration of cells. HIF-1 is a heterodimer composed of the inducible HIF-1alpha and the constitutively expressed HIF-1beta/ARNT subunits. Using villous explants, we have demonstrated that the oxygen-regulated events of early trophoblast differentiation are in part mediated by TGFbeta(3), an inhibitor of trophoblast differentiation, via HIF-1alpha. Pre-eclampsia is a disease of pregnancy that is characterized by shallow trophoblast invasion. Recently, we have reported that TGFbeta(3) is over-expressed in pre-eclamptic pregnancy and that its down-regulation restores invasive capability to trophoblast cells. Because TGFbeta(3) is downstream of HIF-1alpha, in the present study we investigated the expression of HIF-1alpha in pre-eclamptic placentae and age-matched controls using in situ hybridization and histochemical analyses. We found that HIF-1alpha mRNA and protein expression are abnormally elevated in pre-eclamptic placental tissue when compared to normal placental tissue. We conclude that pre-eclampsia may result from a developmental failure of oxygen to increase or of trophoblast cells to respond and/or sense an increase in oxygen. This will prevent the normal TGFbeta3 down-regulation and will lead to poor trophoblast invasion predisposing the pregnancy to pre-eclampsia.

Adult↗
PubMed2002

Oxygen regulation of placental 11 beta-hydroxysteroid dehydrogenase 2: physiological and pathological implications.

Preeclampsia (PE) is a major cause of maternal and perinatal morbidity and mortality. The genesis of PE is related to deficient trophoblast invasion of maternal spiral arteries, which might result in a reduction of placental (PL) oxygen (O(2)). An absence of increased O(2) that normally occurs around the 10-12th wk of gestation results in aberrant expression of genes that might contribute to the pathophysiology of PE. We examined the expression and regulation of PL 11 beta-hydroxysteroid dehydrogenase 2 (11 beta-HSD) in normal pregnancies and in PE. Two types of 11 beta-HSD exist in the placenta, 11 beta-HSD1 and 11 beta-HSD2. 11 beta-HSD2 is thought to protect the fetus from cortisol excess. In PE, both the expression and activity of PL 11 beta-HSD2 were reduced significantly compared with those in age-matched controls. As PE is associated with a reduction of PL O(2), we next investigated whether in normal pregnancy 11 beta-HSD2 expression changes at the time of the increase in O(2). 11 beta-HSD2 was detected as early as 5 wk, with expression limited to the syncytiotrophoblast (ST). At 10-12 wk, this expression increased and was also found in the cytotrophoblast and extravillous trophoblast. These results were substantiated by Western blot. The ability of O(2) to regulate 11 beta-HSD2 was determined both in cultures of villous explant from early gestation and in term trophoblast cells after incubation under 3% or 20% O(2). Villous explants cultured under 20% O(2) showed higher enzyme activity and expression compared with 3% O(2). Term trophoblast cells also exhibited higher enzyme activity at 20% vs. 3% O(2). No change in 11 beta-HSD1 expression was observed in early pregnancy or in PE. This is the first report to suggest that 11 beta-HSD2 is O(2) dependent in first and third trimester placenta during human gestation.

11-beta-Hydroxysteroid Dehydrogenase Type 2↗
PubMed2001

Focal adhesion kinase is a key mediator of human trophoblast development.

Trophoblast differentiation during the first trimester of pregnancy involves cell proliferation and invasion and extracellular matrix (ECM) remodeling. Reports have indicated that, in a variety of cell types, processes such as proliferation, invasion, and ECM remodeling require the turnover of focal adhesions mediated by a cytoplasmic tyrosine kinase named focal adhesion kinase (FAK). Therefore, in the present study we examined the expression and spatial localization of FAK during early human placental development. Immunocytochemical and immunoblot analysis showed that FAK and a focal adhesion-associated protein named paxillin were highly expressed between the 5th and 8th weeks of gestation, specifically in villous cytotrophoblast and extravillous trophoblast (EVT) cells. Activated FAK, phosphorylated on Tyr-397, colocalized with alpha5 integrin and matrix metalloproteinase-2 (MMP2) expression in EVT cells within a previously characterized intermediate, invasive-restrained region. FAK and paxillin expression dramatically decreased after 10 to 12 weeks of gestation coincident with increasing pO(2) levels. Exposure of human villous explants of 5 to 8 weeks to a 3% O(2) environment resulted in increased trophoblast outgrowth, cell proliferation, and detection of alpha5 integrin and MMP2, as well as increased activation of FAK in EVT cells compared with explants grown in a 20% O(2) environment. To determine whether FAK was a key requisite for trophoblast differentiation, villous explants of 5 weeks gestation were grown in Matrigel in a 3% O(2) environment and incubated with 20-mer antisense FAK oligonucleotides. A dramatic reduction of trophoblast outgrowth was observed in antisense-treated explants compared with missense and control cultures, and, in addition, cell proliferation and MMP2 activity in antisense-treated explants were dramatically reduced. These data suggest that FAK is a key kinase involved in early trophoblast cell differentiation and plays a role in regulating cell proliferation and motility during early placental development.

Antisense Elements (Genetics)↗
PubMed2000

Posttranscriptional regulation of human leukocyte antigen G during human extravillous cytotrophoblast differentiation.

Human maternal tolerance to a semiallogenic fetus may be maintained, in part, by the unusual expression pattern of antigen-presenting molecules in placental trophoblast cells. Extravillous cytotrophoblast (EVC) cells, which invade the maternal decidua, express high levels of human leukocyte antigen G (HLA-G), a nonclassical, major histocompatibility complex (MHC) class I molecule. HLA-G transcripts have been detected in tumors and other tissues, yet protein accumulation is rare. We show that, within EVC cells themselves, the mRNA is more broadly expressed than the protein. Specifically, accumulation of HLA-G protein was markedly delayed during EVC cell differentiation. To elucidate this mechanism, we performed a comprehensive analysis comparing the expression of HLA-G and proteins essential for MHC class I expression at the cell surface. The transporter for antigen processing proteins TAP1 and TAP2, as well as tapasin and beta(2)-microglobulin, appeared to be coordinately expressed throughout EVC cell columns. Strikingly, they all accumulated well in advance of the HLA-G protein but concurrently with its mRNA. A similar delay in the accumulation of the HLA-G protein was observed in vitro, using cultures of chorionic villi. We conclude that posttranscriptional regulation of HLA-G is fundamental to EVC cell development and is achieved independently of the peptide loading system. This represents a novel mechanism of MHC class I regulation.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed2000

Hypoxia-inducible factor-1 mediates the biological effects of oxygen on human trophoblast differentiation through TGFbeta(3)

During early pregnancy, placentation occurs in a relatively hypoxic environment that is essential for appropriate embryonic development. Intervillous blood flow increases around 10 to 12 weeks of gestation and results in exposure of trophoblast cells to increased oxygen tension. Before this time, low oxygen appears to prevent trophoblast differentiation toward an invasive phenotype. Using human villous explants of 5-8 weeks' gestation, we found that low oxygen tension triggered trophoblast proliferation, fibronectin synthesis, alpha(5) integrin expression, and gelatinase A activity. These biochemical markers were barely detectable under oxic conditions. We therefore examined the placental expression of hypoxia-inducible factor-1 (HIF-1), a master regulator of oxygen homeostasis, and determined that expression of HIF-1alpha subunit during the first trimester of gestation parallels that of TGFbeta(3), an inhibitor of extravillous trophoblast differentiation. Expression of both molecules is high in early pregnancy and falls around 9 weeks of gestation, when placental pO(2) levels are believed to increase. Increasing oxygen tension induced a similar decrease in expression in cultured explants. Moreover, antisense inhibition of HIF-1alpha expression in hypoxic explants inhibited expression of TGFbeta(3), arrested cell proliferation, decreased alpha(5) expression and gelatinase A activity, and triggered biochemical markers of an invasive trophoblast phenotype such as alpha(1) integrin and gelatinase B expression. These data suggest that the oxygen-regulated early events of trophoblast differentiation are in part mediated by TGFbeta(3) through HIF-1 transcription factors.

Cell Differentiation↗
PubMed1999

Inhibition of TGF-beta 3 restores the invasive capability of extravillous trophoblasts in preeclamptic pregnancies.

Preeclampsia, the major cause of maternal morbidity and mortality in developed countries, is associated with abnormalities of placenta function due to shallow invasion of the maternal decidua by trophoblasts. Data suggest that TGF-beta may play a role in inhibiting trophoblast outgrowth or invasion, or both. We report that placental TGF-beta 3 expression is high in early pregnancy but falls at around 9 weeks' gestation. This pattern is inversely correlated with trophoblast outgrowth and fibronectin synthesis, markers of early trophoblast differentiation toward an invasive phenotype. We demonstrate that TGF-beta 3 is overexpressed in preeclamptic placentae. In contrast to control placentae, explants from preeclamptic pregnancies fail to exhibit spontaneous invasion in vitro. Significantly, antisense-induced inhibition of TGF-beta 3 expression, and inhibition of TGF-beta 3 activity with antibodies, induces the formation of columns of trophoblast cells, which migrate out of the explant into the underlying Matrigel. To our knowledge, this is the first demonstration that the hypoinvasive placental phenotype characteristic of preeclampsia can be essentially normalized in vitro by biochemical manipulation. We speculate that a failure to downregulate expression of TGF-beta 3 at around 9 weeks' gestation results in shallow trophoblast invasion and predisposes the pregnancy to preeclampsia.

Cell Differentiation↗
PubMed1998

PDGF-induced glycosaminoglycan synthesis is mediated via phosphatidylinositol 3-kinase.

Platelet-derived growth factor (PDGF)-BB has been shown previously to increase glycosaminoglycan (GAG) synthesis but not DNA synthesis in freshly isolated fetal lung fibroblasts. In the present study, we found that PDGF-BB also enhanced 35SO4 incorporation into the small, soluble proteoglycan biglycan without affecting biglycan's core protein mRNA expression, suggesting that PDGF-BB mainly affects GAG chain elongation and/or sulfation. PDGF-BB-stimulated GAG synthesis was abrogated by tyrphostin 9, a PDGF receptor-associated tyrosine kinase inhibitor, implying that the stimulatory effect is mediated via the PDGF beta-receptor (PDGFR). The intracellular signal transduction pathways that mediate PDGF-BB-stimulated GAG synthesis in fetal lung fibroblasts were investigated. On ligand-induced tyrosine phosphorylation, PDGFR associated with phospholipase C (PLC)-gamma 1, Ras GTPase activating protein (RasGAP), and phosphatidylinositol 3-kinase (PI3K) but not with the Syp-growth factor receptor-bound protein 2-Son of Sevenless complex. Association of PDGFR with PLC-gamma 1 and RasGAP followed by their tyrosine phosphorylation failed, however, to activate PLC-gamma 1, protein kinase C (PKC), and Ras. Neither a PLC-gamma inhibitor, U-73122; a PKC inhibitor, calphostin C; nor a mitogen-activated protein kinase kinase inhibitor, PD-98059, inhibited PDGF-BB-induced GAG synthesis. In contrast, PDGF-BB stimulation triggered PDGFR-associated PI3K activity. Both PDGF-BB-induced PI3K activation and GAG synthesis were abolished by the PI3K inhibitors wortmannin and LY-294002. The results suggest that PI3K is a downstream mediator of PDGF-BB-stimulated GAG synthesis in fetal rat lung fibroblasts.

Animals↗
PubMed1997

Endoglin regulates trophoblast differentiation along the invasive pathway in human placental villous explants.

Successful invasion of the maternal vascular system by trophoblast cells is a prerequisite for the establishment of a normal hemochorial placenta. Transforming growth factor-beta (TGFbeta) has been implicated in the regulation of trophoblast invasiveness into the uterus. Endoglin is a component of the TGFbeta receptor complex that binds beta1 and beta3 isoforms and is expressed at high levels on syncytiotrophoblast throughout pregnancy and is also transiently up-regulated on extravillous trophoblasts differentiating along the invasive pathway. We investigated the role of endoglin in a serum-free human villous explant culture system that allows the study of trophoblast outgrowth, migration, and invasion and mimics events occurring in anchoring villi during the first trimester of gestation. Addition to explant cultures from 5-8 weeks gestation of a monoclonal antibody to endoglin or of antisense endoglin oligonucleotides significantly stimulated trophoblast outgrowth and migration. These responses were specific, as incubation of explants with nonimmune IgG or sense and scrambled oligonucleotides had no effect. Antisense endoglin-induced trophoblast outgrowth and migration were accompanied by cell division of villous-associated trophoblasts within the proximal region of the forming column and by the characteristic switch in integrins observed in anchoring villi in situ. Treatment of villous explants with antibody and antisense oligonucleotides to endoglin also resulted in an increased fibronectin release into the culture medium. The stimulatory effect of antisense endoglin on fibronectin production was overcome by the addition of exogenous TGFbeta2, but not TGFbeta1 and -beta3. These findings suggest that endoglin expression in the transition from polarized to nonpolarized trophoblasts in anchoring villi is necessary for mediation of the inhibitory effect of TGFbeta1 and/or TGFbeta3 on trophoblast differentiation along the invasive pathway.

Antibodies↗
PubMed1997

Activin is a local regulator of human cytotrophoblast cell differentiation.

Cytotrophoblast cells of the first trimester placenta are highly invasive when removed from villi and cultured in vitro. In vivo, however, only selected cytotrophoblast cells break through the overlying syncytiotrophoblast to form cytotrophoblast columns and ultimately invade the endometrium. To explore the role of paracrine growth factors in regulating cytotrophoblast development, we cultured explants of first trimester chorionic villi in vitro. Both activin and inhibin, as well as the activin binding protein follistatin, are produced by various trophoblast cells throughout pregnancy. We found that addition of activin-A, but not inhibin-A, stimulated the outgrowth of cytotrophoblast cells into the surrounding matrix. This outgrowth was characteristic of that observed in extravillous cytotrophoblast cells in vivo; it was accompanied by cell division within the proximal region of the cytotrophoblast outgrowth, synthesis of fibronectin, as well as the expression of markers characteristic of invasive cytotrophoblast cells, human leukocyte antigen-G and matrix metalloproteinase (MMP)-9. Activin also specifically induced the early expression of MMP-2 within villous cytotrophoblast cells. Addition of the activin binding protein, follistatin, blocked all of the effects of exogenous activin. The morphological and biochemical effects of activin were similar to those observed when signaling of endogenous transforming growth factor-beta was blocked. Interestingly, the latter effects were also reversed by the addition of follistatin. These data suggest that activin plays a local role in promoting cytotrophoblast column formation, likely by regulating the differentiation of villous cytotrophoblast into extravillous cytotrophoblast cells.

Activins↗
PubMed1996

Fetal lung fibroblasts selectively down-regulate proteoglycan synthesis in response to elevated oxygen.

Cell proliferation is in part regulated by extracellular matrix. Therefore, it is possible that elevated O2 may indirectly affect lung fibroblast growth via modulation of extracellular matrix. In the present study, we investigated the effect of elevated O2 on the synthesis of glycosaminoglycans (GAGs) and proteoglycans (PGs) by fetal lung fibroblasts. A 48-h exposure to >/=50% O2 reduced the incorporation of [3H]glucosamine and 35SO4 into GAGs by fetal lung fibroblasts. The relative proportion of the individual GAG molecules was not altered by elevated O2. Fibroblasts exposed to 50% O2 secreted less [35S]proteoglycans into the medium than controls. Specifically, the synthesis of the small soluble PG, biglycan, was decreased by exposure to 50% O2. Fetal lung fibroblasts did not synthesize the small chondroitin/dermatan sulfate PG, decorin. Elevated O2 concentrations also reduced the synthesis of membrane- and matrix-associated PGs. Furthermore, exposure of fetal lung fibroblasts to >/=50% O2 resulted in a decreased mRNA expression for biglycan and versican core protein sequences. In contrast, elevated O2 increased the message for type I collagen and fibronectin without affecting that of beta-actin. The inhibitory effect of elevated O2 on biglycan mRNA and protein expression was overcome by incubating the cells in 3% O2 after the 48-h exposure to 50% O2. The latter treatment also reversed the increased mRNA expression of type I collagen associated with elevated O2 but not that of fibronectin. These results demonstrate that fetal lung fibroblasts, in response to elevated oxygen concentrations, selectively down-regulate their GAG and PG synthesis and that this O2 effect is reversible.

Animals↗
PubMed1996

Identification of receptors binding fibronectin and laminin on fetal rat lung cells.

Fibronectin and laminin have been implicated in regulating lung morphogenesis. In the present study, the cell surface receptors involved in fetal lung cell binding to laminin and fibronectin were identified. Messages for alpha5- and beta1-integrin subunits were detected in both fetal lung epithelial cells and fibroblasts. The presence of alpha5 beta1 -integrin on both cell types was demonstrated by immunocytochemistry and confirmed by cell adhesion experiments with fibronectin and RGD-containing peptides. Epithelial cells adhered more readily to laminin than fibroblasts. The alpha4 beta1-integrin, and RGD-independent fibronectin receptor, was weakly expressed on either cell type. Both cell types expressed alpha6-integrin subunit mRNA and stained immunopositive for the alpha6-subunit. Although either cell type expressed nonintegrin 67-kDa laminin-elastin receptor mRNA, no positive immunoreactivity for this laminin-elastin binding protein was detected. None of these findings explain the enhanced attachment of distal fetal lung epithelial cells to laminin compared with fibroblasts. Previously, we have reported that epithelial cells were enriched in alpha3-integrin subunit mRNA and protein expression. Herein, we found that epithelial cell attachment to laminin was nearly completely inhibited by alpha3- but only partially by alpha6 -monoclonal antibodies. A peptide near the globular region at the long arm of the laminin A-chain, which contained the IKVAV sequence, and the laminin A-chain amino acid sequence representing the alpha3 beta1 -integrin binding site, inhibited the adherence of epithelial cells to laminin. Fetal lung epithelial cells attached to substrata coated with the alpha3 beta1-integrin binding site peptide and the peptide containing the IKVAV sequence. These data suggest that both fetal lung cell types bind to fibronectin via the fibronectin receptor, alpha5 beta1, and fetal lung epithelial cells interact with laminin via alpha3 beta1 and proteins that recognize the IKVAV-containing sequence on the laminin A-chain.

Amino Acid Sequence↗
PubMed1996

Mechanical strain induces constitutive and regulated secretion of glycosaminoglycans and proteoglycans in fetal lung cells.

We have previously shown that an intermittent strain regimen, which simulates fetal breathing movements, enhanced mixed fetal rat lung cell proliferation in organotypic culture. As glycosaminoglycans (GAGs) and proteoglycans (PGs) may modulate growth factor activities, we investigated the effect of intermittent strain on the formation and secretion of GAGs and PGs. Mechanical strain increased the incorporation of [3H]glucosamine and 35SO4 into GAGs and promoted the release of GAGs into the medium. The composition of the individual GAG molecules was not altered by strain. Mixed fetal lung cells subjected to strain secreted more [35S]biglycan into the medium than static controls but biglycan mRNA expression was not significantly altered. As mechanical strain primarily affected the secretion of GAGs and PGs, we then investigated which secretory pathways were stimulated by strain. Fetal lung cells secreted GAGs mainly through a constitutive (basal) pathway which was stimulated by strain. In contrast to static cultures, strain-induced constitutive secretion was partially blocked by the cytoskeletal disruptors colchicine and cytochalasin B, but not by the small G-protein inhibitors N-acetyl-S-farnesyl-L-cysteine and perillic acid. This result suggests that strain-induced constitutive export of GAGs depends on the functional integrity of the cytoskeleton. Strain also triggered the regulated secretion of GAGs. The strain-induced regulatory pathway in fetal lung cells was blocked by ionomycin, BAPTA/AM and gadolinium, suggesting that strain stimulated the regulatory pathway by inducing a rapid calcium influx via a stretch-activated ion channel. We conclude that mechanical strain of mixed fetal lung cells stimulates GAG and PG exocytosis via activation of both the regulated and constitutive pathways.

Animals↗
PubMed1995

Differential expression of collagen-binding receptors in fetal rat lung cells.

Interactions of cells with molecules of the extracellular matrix (ECM) are mediated via specific cell surface receptors. Because collagen is an important ECM component in the developing lung, we investigated the expression of collagen receptors by distal fetal lung epithelial cells and fibroblasts. Cell attachment experiments revealed that fibroblasts but not epithelial cells adhered to various types of collagen. With the use of subunit-specific antibodies, we demonstrated the presence of the collagen integrins alpha 1 beta 1, alpha 2 beta 1, and alpha 3 beta 1 at the fibroblast surface but only the integrin alpha 3 beta 1 on epithelial cells. Affinity chromatography on collagen-Sepharose identified only alpha 1 beta 1 and alpha 2 beta 1 as collagen-binding integrins in extracts of 125I surface-labeled fibroblasts. No collagen-binding receptors were detected in extracts of surface-iodinated epithelial cells. Message for alpha 1- and alpha 2-integrin was readily demonstrated for fibroblasts, but both mRNAs were hardly detectable in epithelial cells. In contrast, epithelial cells expressed significantly greater alpha 3 mRNA levels than fibroblasts. These data demonstrate that alpha 1 beta 1- and alpha 2 beta 1-integrins function as collagen-binding receptors in fetal lung fibroblasts. Distal fetal lung epithelial cells do not express the alpha 1 beta 1- and alpha 2 beta 1-integrins and do not adhere to collagen. The alpha 3 beta 1-integrin, which is expressed by both cell types, does not function as a collagen receptor.

Animals↗