Altered TGF-β Signalling in Inflammatory Nasal Polyps Drive Remodelling in Crswnp

Rationale: Dysregulation of TGF-b and activin signalling play fundamental roles in lower airways remodelling.  This study focuses on characterising remodelling changes seen in CRSwNP and accompanying alteration in TGF-b signalling.

Methods: Immunohistochemical staining was performed on inferior turbinate and nasal polyp biopsy specimens measuring TGF-beta₁, activin-A and its receptor ALK-4, and phosphorylated SMAD₂in subjects with CRSwNP (n=10) and healthy controls (n=19).  Staining for D2-40 and CD34 were used to define lymphatic and vascular remodelling; smooth muscle actin and HSP-47 to study collagen synthesis and myofibroblast transformation.  Matrix metalloprotease7/9 with their inhibitor TIMP-1 were enumerated.  Basement membrane thickness was defined using Siris red stain. 

Results: Basement membrane zone was markedly thinned in both polyp and turbinates of CRSwNP (p<0.01 versus controls). Turbinates show increased lymphatic and vascular remodelling with polyps nearly devoid of glands and possessing very little blood vessels as demonstrated by differences in total CD31/ D2-40 cell counts (p<0.01, p=0.01), blood vessels (p<0.01, p=0.02), vessel size (p<0.01, p=0.04), or vascularity (p=0.02, p=0.25).  HSP-47 expression is elevated in polyps (p=0.09) whilst SMA is increased in turbinates (p=0.03).  MMP7/9: TIMP-1 ratios are elevated in turbinates.  TGF-b expression is increased in polyps (p<0.01) with ALK-4 elevated in polyps and turbinates (p=0.02 and p=0.03).  Activin levels tend to be higher in polyps CRSwNP (p=0.08). 

Conclusions: This data demonstrates remodelling alterations in both polyps and turbinates of CRSwNP.  It is possible that dysregulated TGF-b signalling in inflammatory polyps drives chronic changes in turbinate architecture thereby resulting in characteristic remodelling in this nasal disease.