The team, led by Shilong Liu and senior author Zhenhua Zhu of the First Affiliated Hospital of Hunan University of Chinese Medicine, began by mining publicly available single-cell RNA sequencing datasets from the Gene Expression Omnibus. After quality control and integration, they analyzed 41 CRSwNP samples and 7 healthy controls, resolving the nasal tissue microenvironment into 13 major cell populations. They then zoomed in on the two compartments most directly responsible for tissue architecture: the epithelium, which forms the mucosal barrier, and the fibroblasts of the underlying lamina propria, which manufacture the extracellular matrix. Epithelial cells resolved into 13 subpopulations and fibroblasts into 8, each defined by distinct functional states.

The compositional shifts they observed were striking and asymmetric. In the epithelial compartment, six of the thirteen subpopulations changed significantly in disease. Inflammatory CXCL8-positive cells and MUC5AC-positive goblet cells expanded, while homeostatic FOXJ1-positive ciliated cells, the workhorses of mucociliary clearance, shrank. Basal-like populations marked by KRT15 and COL17A1 grew, signaling a tissue locked into a perpetual injury-repair mode. Fibroblasts shifted more modestly, but the direction was telling: inflammatory CCL2-positive fibroblasts increased while APOD-positive homeostatic fibroblasts declined. The epithelium, in other words, tilted toward inflammation and aberrant secretion, while the stroma edged toward activation.

Differential expression and gene set enrichment analysis deepened the story. Diseased epithelial cells upregulated genes tied to injury responses and remodeling, including SERPINB4, KRT13, MMP7, and VIM, while losing genes that maintain barrier function and ciliary differentiation such as SCGB1A1, FOXJ1, and MUC5B. Enriched pathways included epithelial-mesenchymal transition, hypoxia, inflammatory response, and TGF-beta and WNT signaling. Fibroblasts showed a complementary profile: POSTN, COL1A2, SERPINE1, and CCL2 rose, while homeostatic genes like PI16 and MFAP4 fell, with collagen metabolism and TGF-beta production prominently enriched. Shared hub genes such as IL6 and SERPINE1 appeared in both cell types, hinting at a common inflammatory and matrix-remodeling program.

Pseudotime analysis using Monocle3 and CytoTRACE2 then reconstructed how these states emerge. Epithelial cells appeared to branch from a secretory starting point toward ciliated, mucous, and injury-repair fates, with homeostatic genes like EPCAM and CDH1 declining along the trajectory while KRT15, COL17A1, and the EMT-associated transcription factor SNAI2 increased. Fibroblasts progressed from quiescent CFD- and APOD-expressing states toward activated, contractile phenotypes marked by TAGLN, POSTN, and MYL9, with collagen genes COL1A1 and COL1A2 peaking in mid-to-late pseudotime. The picture is one of gradual, coordinated drift away from tissue homeostasis rather than an abrupt switch.

The most consequential findings came from CellChat, a computational framework that infers ligand-receptor communication between cell populations. In CRSwNP, the overall communication network grew denser and stronger, with two modules standing out. The COLLAGEN module, built on pairs such as COL1A1 and COL1A2 binding CD44, SDC4, and integrins, flowed predominantly from activated fibroblast subpopulations toward specific epithelial subsets. The TGF-beta module, involving TGFB1 binding TGFBR1/TGFBR2 and ACVR1, was more bidirectional, with epithelial and fibroblast compartments signaling reciprocally. Extending the analysis to myeloid cells, the team found that TGFB1 transcripts concentrated in a GPNMB-expressing macrophage state, marked by SPP1, TREM2, and MMP9, that was significantly expanded in polyps, echoing scar-associated macrophages described in fibrotic liver and other tissues.

Crucially, the computational predictions held up at the protein level in human tissue. Examining nasal polyps from three patients and control mucosa from three individuals undergoing septal surgery, the researchers used Masson’s trichrome staining and tyramide signal-amplified immunofluorescence. Polyps showed denser subepithelial collagen deposition, stronger COL1A1 and alpha-SMA signals in the lamina propria, nuclear accumulation of phosphorylated Smad3 in epithelial cells, weakened E-cadherin, and increased N-cadherin and periostin, all statistically significant. One particularly revealing observation concerned architecture rather than abundance: in healthy mucosa, COL1A1 and periostin formed a compact, continuous band beneath the epithelium, but in polyps this band became loose and discontinuous, with matrix proteins diffusing into the lamina propria. Remodeling in CRSwNP, the data suggest, involves not just more matrix but disorganized matrix.

To test causality in a living system, the team established a CRSwNP-like mouse model using intranasal ovalbumin challenge combined with Staphylococcus aureus enterotoxin B, a superantigen long implicated in polyp formation. Over roughly four months, model mice developed thickened respiratory epithelium, polypoid protrusions, inflammatory infiltration, and significantly increased subepithelial collagen by Sirius Red staining under polarized light. Immunofluorescence mirrored the human findings: alpha-SMA-positive cells accumulated with COL1A1 deposition, epithelial E-cadherin fell, nuclear p-Smad3 rose, and N-cadherin and periostin increased. Western blotting confirmed elevated COL1A1, POSTN, N-cadherin, alpha-SMA, and an increased p-Smad3 to total Smad3 ratio.

The therapeutic implications emerged when the researchers treated model mice with dexamethasone, the corticosteroid that remains first-line therapy for CRSwNP. The drug partially reversed the remodeling phenotype: alpha-SMA and E-cadherin returned to levels statistically indistinguishable from controls, while COL1A1, POSTN, and N-cadherin declined but stayed above baseline. The p-Smad3/Smad3 ratio showed only a non-significant downward trend. This partial response is mechanistically coherent, since the glucocorticoid receptor is known to directly inhibit the transcriptional activation function of Smad3, but it also carries a sobering message: broad anti-inflammatory treatment alone may not fully reverse established structural remodeling, and pathway-targeted anti-fibrotic strategies deserve exploration.

The authors are careful about the limits of their work. CellChat and pseudotime analyses are computational inferences that nominate candidate signaling axes rather than prove physical ligand-receptor engagement, and no knockdown, pathway blockade, or co-culture experiments were performed. The two public cohorts differ in ethnicity and inflammatory endotype, one skewed toward Type 2 inflammation and the other toward IL-1beta-driven myeloid inflammation, and eosinophils, classic sources of TGF-beta1 in polyps, were too sparsely captured for subcluster analysis. Yet the reproducible detection of the same epithelial-fibroblast TGF-beta/Smad axis across cohorts differing in platform, ancestry, and sampling site argues that it is a shared feature of polyp remodeling rather than a cohort-specific artifact. If future spatially resolved and functional studies confirm this circuit, the collagen and TGF-beta dialogue between epithelium and stroma could become a tractable target for therapies aimed not just at shrinking polyps, but at preventing the scarring that makes them return.

Subject of Research: TGF-beta/Smad-mediated epithelial-fibroblast remodeling and collagen deposition in chronic rhinosinusitis with nasal polyps

Article Title: TGF‐β/Smad‐Associated Epithelial–Fibroblast Remodeling Underlies Collagen Deposition in Chronic Rhinosinusitis With Nasal Polyps

Article References: Liu, S., Xie, P., Deng, H., & Zhu, Z. (2026). TGF‐β/Smad‐Associated Epithelial–Fibroblast Remodeling Underlies Collagen Deposition in Chronic Rhinosinusitis With Nasal Polyps. Immunity, Inflammation and Disease, 14(10), Article e70532. https://doi.org/10.1002/iid3.70532

Image Credits: AI Generated

DOI: 10.1002/iid3.70532

Keywords: chronic rhinosinusitis, nasal polyps, TGF-beta, Smad3, fibroblasts, epithelial-mesenchymal transition, collagen deposition, single-cell RNA sequencing, CellChat, macrophages, dexamethasone, tissue remodeling

Chronic rhinosinusitis is one of the most common chronic inflammatory conditions of the airways, affecting a substantial share of adults worldwide and imposing significant quality-of-life and economic burdens. It is defined by persistent inflammation of the mucosa lining the nose and paranasal sinuses, and it is classified into clinical phenotypes such as disease with or without nasal polyps under the European Position Paper on Rhinosinusitis and Nasal Polyps 2020 criteria. Despite its prevalence, the immunological mechanisms driving the disease remain incompletely understood, and one intriguing line of investigation has focused on the unexpected role of taste receptors in airway defense.

The science behind that line of research is genuinely striking. In 2009, a landmark study showed that the motile cilia of human airway epithelial cells are chemosensory, meaning they can detect chemicals in their environment. T2R38, the receptor encoded by TAS2R38, recognizes acyl-homoserine lactones, which are quorum-sensing molecules that bacteria use to communicate and coordinate the formation of biofilms. When T2R38 binds these bacterial signals, it triggers a cascade that produces nitric oxide within the epithelial cells. Nitric oxide, in turn, stimulates the cilia to beat faster and directly harms bacteria, accelerating mucociliary clearance, the conveyor-belt mechanism that sweeps mucus and trapped microbes out of the airways. In other words, the same receptor that lets people perceive the bitterness of compounds such as those in cruciferous vegetables also functions as a microbial sentry in the nose.

This dual role has clinical consequences. Previous work has linked T2R38 receptor polymorphisms to susceptibility to upper respiratory infections and to chronic rhinosinusitis requiring surgery, and genotype has even been reported to predict surgical outcomes in certain disease subtypes. Other studies have examined T2R38 expression and function in diseased sinus tissue and nasal polyps. But a methodological question has hovered over this entire literature: if researchers biopsy one anatomical site, say the inferior turbinate, can they generalize the measured TAS2R38 expression to the rest of the sinonasal cavity? If expression varied substantially between the maxillary, ethmoid, frontal, and sphenoid sinuses, or between polypoid and non-polypoid tissue, then sampling location could silently bias results and make studies from different centers difficult to compare.

To settle the question, the Vietnamese team designed a prospective cross-sectional study embedded in routine endoscopic sinus surgery. They recruited 67 patients with chronic rhinosinusitis diagnosed according to the EPOS 2020 criteria and harvested mucosal specimens from up to six anatomical sites in each patient: the inferior turbinate, the maxillary sinus, the ethmoid sinus, the frontal sinus, the sphenoid sinus, and nasal polyps when present. They also collected 29 non-inflammatory septal specimens as controls. In total, 337 mucosal samples were collected, an unusually dense spatial sampling of a single patient population for this kind of molecular study.

The molecular measurements followed rigorous standards. Relative TAS2R38 messenger RNA expression was quantified by reverse transcription quantitative polymerase chain reaction, or RT-qPCR, performed in accordance with the MIQE guidelines, the internationally accepted quality framework for quantitative PCR experiments, and normalized to the housekeeping gene GAPDH. After strict quality control, which excluded 84 specimens because of cycle threshold values outside acceptable limits or minute fibrous tissue yields, 253 valid specimens from 55 patients remained for analysis. The final dataset included 52 inferior turbinate samples, 50 maxillary samples, 49 ethmoid samples, 44 polyp samples, 43 frontal samples, and 15 sphenoid samples.

The analytical approach was as important as the sampling design. Because multiple biopsies came from the same patient, the data points are statistically clustered, and treating them as independent would inflate false confidence. The researchers therefore used linear mixed-effects modeling with patient-specific random intercepts as their principal framework, a technique that explicitly separates variation between individuals from variation within individuals across anatomical sites. They supplemented this with sensitivity analyses and fold-difference calculations based on the standard 2 to the power of negative delta delta Cq method.

The results were unambiguous. Mean delta Cq values, a measure inversely related to gene expression, were remarkably comparable across subsites, ranging only from 2.06 to 2.81, and an exploratory analysis of variance found no significant differences among sites. In the principal mixed-effects model, anatomical sampling site showed no statistically significant association with TAS2R38 expression. Crucially, the variance decomposition told the deeper story: inter-individual biological variance substantially exceeded intra-individual spatial variation, with an intraclass correlation coefficient of 0.333, meaning roughly a third of the variance in expression was attributable to differences between patients rather than differences between locations within a patient. The robustness of the conclusion held across six sensitivity scenarios, including the exclusion of the small sphenoid subset and multivariable adjustments for age and sex.

One exploratory observation adds biological intrigue. Diseased mucosa demonstrated an approximately 2.48-fold upregulation of TAS2R38 relative to non-site-matched septal controls, hinting that the inflammatory environment of chronic rhinosinusitis may itself alter the expression of this chemosensory defense receptor. The authors characterize this comparison as exploratory, and the control tissue was not matched to the disease sites, so it should be interpreted with appropriate caution. Still, it aligns with a growing body of work suggesting that the bitter taste receptor system is dynamically involved in airway inflammation rather than being a static genetic fixture.

The practical implications reach well beyond the operating theater. For translational airway researchers, the study provides evidence that inferior turbinate biopsy, one of the simplest and most accessible sampling procedures in the nose, could serve as a pragmatic surrogate for investigating sinonasal chemosensory innate defense, sparing patients and researchers the complexity of multi-site sampling. For clinicians, the finding reinforces the idea that a patient’s individual biology, including their TAS2R38 genotype and expression profile, may matter more for disease susceptibility and treatment response than the specific anatomy involved. And for the broader field of innate immunity, it adds a methodological anchor to a rapidly evolving story about how the airways borrow the molecular machinery of taste to defend themselves against microbial invaders. As research into bitter receptor-based therapies for airway disease continues to gather momentum, knowing that one well-chosen biopsy can speak for the whole cavity removes a persistent source of uncertainty from the evidence base.

Subject of Research: TAS2R38 bitter taste receptor gene expression across sinonasal anatomical sites in chronic rhinosinusitis

Article Title: Anatomical sampling site is not associated with TAS2R38 gene expression in chronic rhinosinusitis: A cross-sectional RT-qPCR study

Article References: Cao, M. T., Luong, T. L. A., & Nguyen, X. N. (2026). Anatomical sampling site is not associated with TAS2R38 gene expression in chronic rhinosinusitis: A cross-sectional RT-qPCR study. Molecular Biology Reports, 53(1), Article 1659. https://doi.org/10.1007/s11033-026-12838-z

Image Credits: AI Generated

DOI: 10.1007/s11033-026-12838-z

Keywords: TAS2R38, bitter taste receptor, chronic rhinosinusitis, nasal polyps, RT-qPCR, linear mixed-effects model, innate immunity, nitric oxide, mucociliary clearance, endoscopic sinus surgery, inferior turbinate, sinonasal mucosa

The molecule in question is maresin 1, or MaR1, a specialized pro-resolving mediator derived from docosahexaenoic acid, the omega-3 fatty acid abundant in fish oil. Specialized pro-resolving mediators were discovered relatively recently in the history of inflammation research, and they overturned a long-standing assumption that the end of an inflammatory response was simply a passive winding down. Instead, scientists led by Charles Serhan and colleagues showed that resolution is an active, orchestrated program, driven by lipid signals such as resolvins, protectins and maresins that recruit the cells needed to clear debris, quieten immune signaling and restore tissue. Maresin 1, produced by macrophages, has attracted particular attention because it both curbs inflammatory signaling and supports tissue regeneration. The question the Turkish team asked was deceptively simple: if MaR1 is the body’s own inflammation terminator, what is it doing in nasal polyps, where inflammation clearly refuses to resolve?

To find out, the researchers, led by Zulkuf Kaya of the Department of Ear, Nose and Throat Diseases at Atatürk University Research Hospital in Erzurum, together with pharmacologists from Atatürk University and Erzincan Binali Yıldırım University, recruited 60 patients. Thirty of them were undergoing endoscopic sinus surgery for nasal polyps, while the other 30, scheduled for rhinoplasty, served as controls and provided healthy nasal mucosa samples. The design is a straightforward case-control comparison, but it gives researchers a rare window into the biochemistry of polyp tissue at the moment it is removed. The work was approved by the Atatürk University Faculty of Medicine Clinical Research Ethics Committee and conducted with written informed consent from all participants, in line with the Declaration of Helsinki.

From each tissue sample the team measured the concentrations of three molecules using enzyme-linked immunosorbent assay, or ELISA, a technique that uses antibodies to quantify specific proteins with high sensitivity. Alongside MaR1, they measured transforming growth factor beta, TGF-β, a cytokine long implicated in tissue remodeling, fibrosis and the chronic wound-like state of polyp tissue, and nuclear factor erythroid 2–related factor 2, Nrf2, the master transcriptional regulator of the cellular antioxidant response. The choice of these three targets reflects a growing view in the field that nasal polyps are not merely an allergic or infectious problem, but a systems-level failure involving oxidative stress, unresolved inflammation and disordered tissue repair.

The results were striking. In the polyp group, the researchers observed that levels of both MaR1 and Nrf2 were significantly increased compared with healthy nasal mucosa, while TGF-β levels were significantly decreased. At first glance, the direction of these changes may seem counterintuitive. If MaR1 resolves inflammation and Nrf2 defends against oxidative damage, why would both be elevated in a tissue that is famously inflamed? The authors suggest that the answer lies in the dynamics of a chronic inflammatory process: the body may be mounting a compensatory response, ramping up its pro-resolving and antioxidant machinery in an attempt to contain the damage, even as the underlying drivers of inflammation persist and overwhelm it.

This interpretation fits with what is known about the biology of each player. Nrf2 normally sits dormant in the cytoplasm, bound to its inhibitor Keap1, until reactive oxygen species or electrophilic stress liberate it to travel to the nucleus and switch on a battery of antioxidant and detoxifying genes. In chronically inflamed tissues, sustained oxidative stress would be expected to activate Nrf2 persistently, and elevated levels have been reported in a range of inflammatory airway diseases. Similarly, TGF-β is a double-edged cytokine: it drives fibrosis and epithelial remodeling, processes central to polyp growth, but its measured abundance in tissue can vary with the stage of disease, the cellular composition of the sample and the interplay with other signaling pathways. A significant decrease in TGF-β in polyp tissue, as observed here, invites questions about how the remodeling program in polyps is regulated and how it might interact with the pro-resolving lipid pathways the team set out to study.

The study’s real contribution may lie in connecting these threads. By measuring MaR1 alongside Nrf2 and TGF-β in the same samples, the researchers have, for the first time in this tissue, laid out a triad of signals that could plausibly form an intracellular circuit: lipid-mediated resolution signals, antioxidant transcriptional responses and profibrotic cytokine activity, all shifting together in polyp pathophysiology. If future work confirms functional links between them, for example whether MaR1 signaling influences Nrf2 activation or modulates TGF-β-driven fibrosis in airway epithelial cells and macrophages, it would open a genuinely new therapeutic axis. Current treatments for nasal polyps, from intranasal and systemic corticosteroids to the newer biologics targeting type 2 inflammation, such as dupilumab, address specific arms of the immune response but do not directly harness the body’s own resolution program.

The idea of resolution-based therapy is one of the more exciting frontiers in inflammation medicine. Animal studies have shown that maresin 1 and related mediators can reduce tissue damage in models ranging from colitis to lung injury, and stable synthetic analogs are being explored as drug candidates. If the elevation of MaR1 in polyp tissue reflects a genuine, if insufficient, attempt at self-resolution, then supplementing that signal, perhaps with inhaled or topical formulations, could in principle help tip the balance from chronic inflammation back toward tissue homeostasis. Conversely, the altered TGF-β profile suggests that any such approach would need to account for the remodeling biology of polyps, not just the inflammatory one. The authors themselves are careful on this point, noting that potential treatments for nasal polyps may be better understood with more comprehensive and well-matched studies.

That caution is warranted. The study is a cross-sectional comparison of tissue removed at surgery, so it captures a snapshot rather than a trajectory, and it cannot establish whether the changes in MaR1, Nrf2 and TGF-β are causes or consequences of polyp formation. The control group, drawn from rhinoplasty patients, is a reasonable comparator but may differ from the polyp group in ways beyond the presence of polyps. ELISA measurements of lipid mediators in tissue are also technically demanding, and the field has learned that careful validation is essential. The authors acknowledge that larger and better-matched cohorts will be needed before the findings can guide clinical decisions. Still, the study was peer-reviewed and published open access in BMC Pharmacology and Toxicology, with the accepted manuscript released in September 2026, and it was supported by Atatürk University’s Scientific Research Projects Coordination Unit.

For patients, the significance of this work is less about immediate new treatments and more about a shift in perspective. Nasal polyps have long been treated as a problem of too much inflammation; this study reframes them, at least in part, as a problem of failed resolution, in which the body’s own peacekeeping molecules are present but apparently not prevailing. Mapping how maresin 1, Nrf2 and TGF-β interact inside the cells of the nasal mucosa could eventually point to biomarkers that identify which patients are most likely to recur after surgery, or to drugs that restore the resolution program the tissue is struggling to complete. The sense of smell, the ability to breathe freely through the nose, and freedom from a cycle of steroids and repeat operations all hang on that molecular balance. This study does not settle it, but it draws the map with considerably more detail than before.

Subject of Research: The role of the pro-resolving lipid mediator maresin 1 and the Nrf2 and TGF-β pathways in nasal polyp pathophysiology

Article Title: Investigation of maresin 1 and possible associated intracellular pathways in nasal polyp pathophysiology

Article References: Kaya, Z., Mutlu, V., Halici, Z., Kaya, Z. K., Ozcelik, A. T., Topatan, E., & Ozcelik, C. (2026). Investigation of maresin 1 and possible associated intracellular pathways in nasal polyp pathophysiology. BMC Pharmacology and Toxicology. https://doi.org/10.1186/s40360-026-01242-9

Image Credits: AI Generated

DOI: 10.1186/s40360-026-01242-9

Keywords: maresin 1, nasal polyps, Nrf2, TGF-β, inflammation resolution, specialized pro-resolving mediators, docosahexaenoic acid, ELISA, chronic rhinosinusitis, oxidative stress, otolaryngology, BMC Pharmacology and Toxicology