Phenotype-specific differences in bone morphogenetic protein ligand expression and intracellular signaling pathway...

Chronic rhinosinusitis (CRS) comprises distinct phenotypes with divergent inflammatory and tissue remodeling patterns. Bone morphogenetic proteins (BMPs) are key regulators of airway repair; however, it remains unclear whether phenotypic differences between CRS with nasal polyps (CRSwNP) and without nasal polyps (CRSsNP) are associated with BMP ligand abundance or downstream pathway activity. We investigated phenotype-specific BMP/Smad pathway patterns and their potential relevance to airway remodeling.

Sinonasal tissue samples were obtained from patients with CRSwNP (n = 20), CRSsNP (n = 16), and control subjects (n = 10). Expression and localization of BMP-2, BMP-4, TGF-β1, Smad1, Smad5, Smad8, and phospho-Smad1/5/8 were evaluated by immunohistochemistry using semi-quantitative H-SCORE analysis. Tissue protein levels of BMP-2, BMP-4, and TGF-β1 were quantified by enzyme-linked immunosorbent assay (ELISA).

CRSsNP tissues demonstrated increased expression of BMP-2, BMP-4, and TGF-β1 compared with controls, consistent with a fibrotic remodeling profile, whereas CRSwNP tissues exhibited reduced ligand expression. In contrast, phospho-Smad1/5/8 expression was significantly increased in both CRS phenotypes relative to controls. These findings suggest that downstream Smad activation may not directly parallel BMP ligand abundance across CRS phenotypes. BMP-4 expression showed a positive association with phospho-Smad1/5/8 levels in both CRS subgroups, whereas BMP-2 did not. ELISA analyses were largely concordant with immunohistochemical findings.

The observed patterns suggest that BMP/Smad pathway activity in CRS may vary according to disease phenotype and tissue context. These findings highlight the importance of interpreting signaling activity alongside ligand expression in tissue-based studies and provide descriptive insight into remodeling-related pathway behavior in CRS.