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Investigating Laminin‐α3β3γ2's Potential Role in Epithelial‐to‐Mesenchymal Transition in Pulmonary Epithelia
Author(s) -
David Joshua,
Blakeney B,
Heise Rebecca
Publication year - 2015
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.29.1_supplement.719.17
Subject(s) - laminin , extracellular matrix , epithelial–mesenchymal transition , microbiology and biotechnology , chemistry , pulmonary fibrosis , cancer research , morphogenesis , fibrosis , pathology , biology , cancer , medicine , metastasis , biochemistry , gene
The extracellular matrix (ECM) provides physical scaffolding for cells but also is essential for many biochemical and biomechanical cues in tissue differentiation and homeostasis. Under normal physiologic conditions, ECM degradation and deposition act in equilibrium. Increased ECM degradation and depostion are processes known to be critical for epithelial‐to‐mesenchymal‐transition (EMT) during the pathogenesis of cancer and fibrosis. The exact mechanism underlying EMT in Idiopathic Pulmonary Fibrosis, however, remains uncertain. There is evidence that ECM cleavage products, including domain 3 of Laminin‐ α3β3γ2 (Laminin‐γ2‐DIII), can activate the Epidermal Growth Factor Receptor (EGFR), due to similar tertiary structure, in many cancers. We hypothesized that Bone Morphogenic Protein‐1 (BMP1), Matrix Metalloproteinase‐2 (MMP2) and Neutrophil Elastase expose Laminin‐γ2‐DIII, which then binds to the EGFR and activates its downstream cascade. Preliminary data of this combination of proteinases and Laminin‐γ2 demonstrates modulation of EMT markers including significant increase of α‐Smooth Muscle Actin (α‐SMA) and significant decrease of E‐Cadherin in A549 cells. Collectively, these results suggest that cleaved Laminin ‐γ2‐DIII may propagate epithelial‐to‐mesenchymal transition in pulmonary epithelia. Future studies will investigate the activation of EFGR by Laminin‐γ2‐DIII in mouse models of pulmonary fibrosis. Research supported by Virginia Commonwealth University Honors College Summer Undergraduate Program JD, NSF CMMI‐1351162 RH.