Expression of Transforming Growth Factor-<i>α</i> in Mid-gestation Human Fetal Lung

Tp, Strandjord; Jg, Clark; Wa, Hodson; Ra, Schmidt; Dk, Madtes

doi:10.1165/ajrcmb/8.3.266

Cited by 35 publications

(7 citation statements)

References 32 publications

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“…TGF␣ is expressed in bronchioles and saccular epithelia in late gestational lungs (Strandjord et al, 1993(Strandjord et al, , 1994(Strandjord et al, , 1995Ruocco et al, 1996). It was reported that the expression is decreased by 50% during the transition from the canalicular (E19 -E20) to the saccular (E21) stage in late-term fetal rat lung (Kubiak et al, 1992).…”

Section: Discussionmentioning

confidence: 99%

HB‐EGF decelerates cell proliferation synergistically with TGFα in perinatal distal lung development

Minami

Iwamoto

Mekada

2007

Developmental Dynamics

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Heparin-binding epidermal growth factor-like growth factor (HB-EGF) is a member of the EGF family of growth factors that is suggested to be involved in distal lung development. In HB-EGF null (HB del/del ) newborns, a histopathologic analysis revealed abnormally thick saccular walls occurring from embryonic day 18.5 that reduced the terminal saccular space area. HB-EGF gene deletion resulted in a significant increase in cell proliferation, indicating that HB-EGF suppresses distal lung cell proliferation. Furthermore, an analysis of saccular morphology and proliferation in HB-EGF and transforming growth factor-␣ (TGF␣) double-mutant newborns revealed that HB-EGF and TGF␣ function synergistically in this suppression. Finally, crosses between HB del/del mice and waved 2 mice, a hypomorphic EGF receptor (EGFR) mutant strain, suggest that HB-EGF and EGFR cooperate in this process. Thus, HB-EGF has a novel suppressive function that contributes to decelerating distal lung cell proliferation synergistically with TGF␣ through EGFR in perinatal distal lung development. Developmental Dynamics 237:247-258, 2008.

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Section: Discussionmentioning

confidence: 99%

HB‐EGF decelerates cell proliferation synergistically with TGFα in perinatal distal lung development

Minami

Iwamoto

Mekada

2007

Developmental Dynamics

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“…EGF mRNA has been detected in isolated adult rat type I1 pneumocytes [28] and TGF-a mRNA in fetal rat lung epithelial cells [48]. In humans, immunoreactive TGF-a has been detected in epithelial cells of prealveolar ducts at 22 weeks of gestation [49], and immunoreactive EGF has been detected in tracheobronchial epithelium from fetal lung before 24 weeks gestation [50] and in bronchial glands from adult lung [51]. Our data, detecting the EGF receptor in differentiating distal pulmonary epithelium agrees with the literature and lends further support to the concept that EGF may act in either an autocrine or paracrine manner during human alveolar type I1 cell differentiation.…”

Section: Discussionmentioning

confidence: 99%

Localization of Epidermal Growth Factor Receptor in Alveolar Epithelium During Human Fetal Lung Development in Vitro

Klein

Fritz

McCarthy

et al. 1995

Experimental Lung Research

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Epidermal growth factor (EGF) enhances alveolar type II cell differentiation. In human fetal lung explants, EGF stimulates surfactant protein A (SP-A) synthesis. This effect may occur through a direct interaction of the ligand on EGF receptors located within distal pulmonary epithelium during alveolar type II cell differentiation. To determine if EGF receptor is present in alveolar epithelium, immunostaining for EGF receptor and in situ hybridization for EGF receptor mRNA were performed in human fetal lung explants undergoing alveolar type II cell differentiation in vitro. After 4 days in culture, EGF receptor immunostaining was present in alveolar epithelium from human fetal lung explants compared to minimal immunostaining in undifferentiated human fetal lung epithelium prior to culture. In situ hybridization revealed increased EGF receptor mRNA in differentiated type II cells from cultured explants, with minimal EGF receptor mRNA detected in undifferentiated epithelium from tissue prior to culture. Immunogold staining revealed EGF receptors on the cytoplasmic membranes of epithelial cells lining the prealveolar ducts in human fetal lung explants after 2 days in culture. Alveolar type II cell differentiation in vitro was confirmed ultrastructurally by the presence of lamellar bodies and biochemically by an increase in SP-A content. Thus, EGF receptor is found in alveolar epithelium during differentiation, which suggests an important role for EGF during human fetal lung development.

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“…Based on data obtained by in vitro studies, it is clear that the proliferation of respiratory epithelium is dependent on a number of growth factors such as the epidermal growth factor (EGF) and insulin (13,14). The endogenous expression of EGF, TGF-␣ , and EGF receptors in normal adult and fetal lung has been demonstrated in several species, suggesting that the respiratory epithelium is capable of autocrine/paracrine growth control (15)(16)(17)(18)(19)(20). The co-expression of EGF and TGF-␣ within the lung is enigmatic since both proteins produce mitogenic effects through the same tyrosine kinase receptor, EGF receptor (21).…”

Section: Introductionmentioning

confidence: 99%