The role of Smoothened in pulmonary pathologies

Mon, 08/15/2016 - 14:24

The Hedgehog (Hh) family of secreted proteins is involved in a number of developmental processes, one of which is the development of cancer. Past data suggests that the Sonic hedgehog (Shh) receptor is composed of two transmembrane proteins, Patched and Smoothened.  The Hedgehog (Hh) signaling pathway is vital to the development of many tissues during embryogenesis, however, it also has an important role after development.  After development, Hh signaling regulates stem cells and their regenerative function.  When the Hh pathway is awry, signaling may turn oncogenic in nature. This has been witnessed in interactions between Patched and Smoothened, where Patch inhibits the function of Smoothened.  When normal Smoothened activity is restricted or mutated, it can cause unregulated activation of the Hh pathway which leads to cancer.  This post will delve into research using a Smoothened antibody to further elucidate its role in pulmonary pathologies. 

smoothened antibody

Immunohistochemistry-Paraffin: Smoothened Antibody [NBP2-24543] - Immunohistochemical analysis of Smoothened in formalin-fixed paraffin-embedded human brain tissue using an isotype control antibody (top) and Smoothened antibody (bottom) at 10 ug/ml.

First, Zhang et al used a Smoothened antibody in their research to determine whether Smoothened gene expression levels directly correlated with survival in patients with mesothelioma.  Malignant mesothelioma is an aggressive form of cancer for which there are limited targeted therapies, therefore improving molecular therapies against this disease is of high concern.  Zhang’s group began by analyzing Smoothened and Hh expression levels in 46 mesothelioma tissue samples in RT-PCR.  Next, they performed peroxidase-based immunohistochemistry using a Smoothened antibody and Hh antibody.  They witnessed a direct correlation between heightened levels of Smoothened gene expression and poor survival, and also found that inhibiting Hh function using a Smoothened inhibitor suppressed cellular proliferation.  This research overall suggests a strong correspondence between Smoothened and Hh expression levels and the survival chances of a patient with mesothelioma. 

Another prominent pulmonary pathology, known as idiopathic pulmonary fibrosis (IPF), also has implications for the role of the Hh pathway and ultimately the Smoothened protein.  Bolaños et al set out to further investigate how the expression of Hh signaling pathway related proteins, Smoothened, Patched and Gli1/Gli2 transcription factors, may contribute to this pathology.  Using a Smoothened antibody in immunohistochemistry it was discovered that Smoothened, alongside Patched, Gli1 and Gli2, were expressed in idiopathic pulmonary fibrosis tissue, but not in wild type lung tissue.  This finding suggests that the Hh pathway is distinctly involved in some way with the development of this form of lung cancer.  However, using a Smoothened antibody they found that Smoothened was the only Hh pathway protein that did not show elevated expression levels in IPF fibroblasts.  Ultimately, after doing further research on Hh pathway proteins on the proliferation of fibroblasts, it was implied that fibroblast resistance to apoptosis might also be a contributing factor to IPF pathology. 

Novus Biologicals offers Smoothened reagents for your research needs including:

PMID: 23379358
PMID: 23023967
PMID: 17139287

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