Growth Factor Control of Growth and Epithelial Differentiation in Embryonic Lungs

1997 ◽  
Vol 60 (1) ◽  
pp. 38-48 ◽  
Author(s):  
Heber C. Nielsen ◽  
Ana Martin ◽  
MaryAnn V. Volpe ◽  
Dimitrios Hatzis ◽  
Robert J. Vosatka
Keyword(s):  
Growth Factor ◽  
Epithelial Differentiation ◽  
Embryonic Lungs

scholarly journals Differentiation of human airway epithelia is dependent on erbB2

2006 ◽  
Vol 291 (2) ◽  
pp. L175-L180 ◽  
Author(s):  
Paola D. Vermeer ◽  
Lacey Panko ◽  
Philip Karp ◽  
John H. Lee ◽  
Joseph Zabner
Keyword(s):  
Growth Factor ◽  
Airway Epithelium ◽  
Human Lung ◽  
Cell Number ◽  
Epithelial Differentiation ◽  
Lung Fibroblasts ◽  
Airway Epithelia ◽  
Human Lung Fibroblasts ◽  
Human Airway ◽  
Human Airway Epithelia

A clinical case documented a reversible change in airway epithelial differentiation that coincided with the initiation and discontinuation of trastuzumab, an anti-erbB2 antibody. This prompted the investigation into whether blocking the erbB2 receptor alters differentiation of the airway epithelium. To test this hypothesis, we treated an in vitro model of well-differentiated human airway epithelia with trastuzumab or heregulin-α, an erbB ligand. In addition, coculturing with human lung fibroblasts tested whether in vivo subepithelial fibroblasts function as an endogenous source of ligands able to activate erbB receptors expressed by the overlying epithelial cells. Epithelia were stained with hematoxylin and eosin and used for morphometric analysis. Trastuzumab treatment decreased the ciliated cell number by 49% and increased the metaplastic, flat cell number by 640%. Heregulin-α treatment increased epithelial height and decreased the number of metaplastic and nonciliated columnar cells, whereas it increased the goblet cell number. We found that normal human lung fibroblasts express transforming growth factor-α, heparin-binding epidermal-like growth factor, epiregulin, heregulin-α, and amphiregulin, all of which are erbB ligands. Cocultures of airway epithelia with primary fibroblasts increased epithelial height comparable to that achieved following heregulin-α treatment. These data show that erbB2 stimulation is required for maintaining epithelial differentiation. Furthermore, the mesenchyme underlying the airway epithelium secretes a variety of erbB ligands that may direct various pathways of epithelial differentiation.

scholarly journals Preclinical evaluation of human secretoglobin 3A2 in mouse models of lung development and fibrosis

2014 ◽  
Vol 306 (1) ◽  
pp. L10-L22 ◽  
Author(s):  
Yan Cai ◽  
Melissa E. Winn ◽  
John K. Zehmer ◽  
William K. Gillette ◽  
Jacek T. Lubkowski ◽  
...  
Keyword(s):  
Growth Factor ◽  
Lung Development ◽  
Therapeutic Agent ◽  
Ex Vivo ◽  
Clinical Settings ◽  
Biochemical Measurement ◽  
Lung Airways ◽  
Further Development ◽  
Embryonic Lungs

Secretoglobin (SCGB) 3A2 is a member of the SCGB gene superfamily of small secreted proteins, predominantly expressed in lung airways. We hypothesize that human SCGB3A2 may exhibit anti-inflammatory, growth factor, and antifibrotic activities and be of clinical utility. Recombinant human SCGB3A2 was expressed, purified, and biochemically characterized as a first step to its development as a therapeutic agent in clinical settings. Human SCGB3A2, as well as mouse SCGB3A2, readily formed a dimer in solution and exhibited novel phospholipase A2 inhibitory activity. This is the first demonstration of any quantitative biochemical measurement for the evaluation of SCGB3A2 protein. In the mouse as an experimental animal, human SCGB3A2 exhibited growth factor activity by promoting embryonic lung development in both ex vivo and in vivo systems and antifibrotic activity in the bleomycin-induced lung fibrosis model. The results suggested that human SCGB3A2 can function as a growth factor and an antifibrotic agent in humans. When SCGB3A2 was administered to pregnant female mice through the tail vein, the protein was detected in the dam's serum and lung, as well as the placenta, amniotic fluids, and embryonic lungs at 10 min postadministration, suggesting that SCGB3A2 readily crosses the placenta. The results warrant further development of recombinant SCGB3A2 as a therapeutic agent in treating patients suffering from lung diseases or preterm infants with respiratory distress.

scholarly journals Cellular therapy of corneal epithelial defect by adipose mesenchymal stem cell-derived epithelial progenitors

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Francisco Bandeira ◽  
Tze-Wei Goh ◽  
Melina Setiawan ◽  
Gary Hin-Fai Yam ◽  
Jodhbir S. Mehta
Keyword(s):  
Stem Cell ◽  
Growth Factor ◽  
Transforming Growth Factor ◽  
Glycogen Synthase ◽  
Anterior Segment ◽  
Corneal Edema ◽  
Epithelial Differentiation ◽  
Corneal Surface ◽  
Cell Based Therapy ◽  
Epithelial Healing

Abstract Background Persistent epithelial defects (PED), associated with limbal stem cell deficiency (LSCD), require ocular surface reconstruction with a stable corneal epithelium (CE). This study investigated CE reformation using human adipose mesenchymal stem cells (ADSC), which derived epithelial progenitors via mesenchymal-epithelial transition (MET). Methods STEMPRO human ADSC were cultured with specific inhibitors antagonizing glycogen synthase kinase-3 and transforming growth factor-β signaling, followed by culture under a defined progenitor cell targeted-epithelial differentiation condition to generate epithelial-like cells (MET-Epi), which were characterized for cell viability, mesenchymal, and epithelial phenotypes using immunofluorescence and flow cytometry. Tissue-engineered (TE) MET-Epi cells on fibrin gel were transplanted to corneal surface of the rat LSCD model caused by alkali injury. Epithelial healing, corneal edema, and haze grading, CE formation were assessed by fluorescein staining, slit lamp bio-microscopy, anterior segment optical coherence tomography, and immunohistochemistry. Results CD73high/CD90high/CD105high/CD166high/CD14negative/CD31negative human ADSC underwent MET, giving viable epithelial-like progenitors expressing δNp63, CDH1 (E-cadherin), epidermal growth factor receptor, integrin-β4, and cytokeratin (CK)-5, 9. Under defined epithelial differentiation culture, these progenitors generated MET-Epi cells expressing cell junction proteins ZO1 and occludin. When transplanted onto rat corneal surface with LSCD-induced PED, TE-MET-Epi achieved more efficient epithelial healing, suppressed corneal edema, and opacities, when compared to corneas without treatment or transplanted with TE-ADSC. CE markers (CK3, 12, and CDH1) were expressed on TE-MET-Epi-transplanted corneas but not in other control groups. Conclusion Human ADSC-derived epithelial-like cells, via MET, recovered the CE from PED associated with LSCD. ADSC can be a viable adult stem cell source for potential autologous epithelial cell-based therapy for corneal surface disorders.

Effects of keratinocyte growth factor on skin epithelial differentiation of human amnion epithelial cells

Burns ◽  
2013 ◽  
Vol 39 (5) ◽  
pp. 905-915 ◽  
Author(s):  
Simat Siti Fatimah ◽  
Geok Chin Tan ◽  
Kienhui Chua ◽  
Ay Eeng Tan ◽  
Abdul Ghani Nur Azurah ◽  
...  
Keyword(s):  
Growth Factor ◽  
Epithelial Cells ◽  
Keratinocyte Growth Factor ◽  
Epithelial Differentiation ◽  
Human Amnion ◽  
Amnion Epithelial Cells
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