Reduction of endocytic activity accelerates cell elimination during tissue remodeling of the Drosophila epidermal epithelium

Introduction: Tissue remodeling refers to structural changes that occur in damaged tissue and is associated with disease severity in asthma. However, the characteristics of tissue remodeling and its prognostic role in chronic rhinosinusitis (CRS) remain unclear. In this report, we evaluated the clinical implications of tissue remodeling in CRS. Methods: We performed a retrospective cohort study of adult patients who underwent endoscopic sinus surgery for bilateral CRS. The histopathology of sinus mucosa was determined by evaluating the inflammatory cell count and tissue remodeling markers (squamous metaplasia, subepithelial gland proliferation, basement membrane [BM] thickening, stromal edema, and fibrosis). Eosinophilic CRS (ECRS) was defined as an eosinophil count >15/high-power field in the biopsied tissue. Patient characteristics, allergy test grade, preoperative Lund-Mackay score (LMS), and pre- and postoperative Lund-Kennedy scores (LKSs) were analyzed. Results: Of the identified patients, 59.1% were classified as ECRS and the remaining 40.9% as non-ECRS. Regarding tissue remodeling markers, stromal edema was seen in 90.9%, BM thickening in 63.6%, and stromal fibrosis in 34.1% of patients. In cases with stromal edema and BM thickening, greater tissue eosinophilia was observed, while stromal fibrosis decreased tissue eosinophilia (p < 0.05). Prognostically, subepithelial gland proliferation alone was an independent risk factor for poor postoperative endoscopic findings (odds ratio: 8.250, 95% confidence interval: 1.128–60.319, p = 0.038). Conclusions: Tissue eosinophilia was commonly associated with BM thickening and stromal edema. Subepithelial gland proliferation predicted a poor surgical prognosis in CRS. These findings imply that tissue remodeling provides additional information not only on the CRS endotype but also on the postsurgical prognosis.

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Dynamics of Galectin-3 serum levels after percutaneous occlusion of the left atrial appendage: a new surrogate parameter for successful LAA closure?

European Heart Journal ◽

10.1093/ehjci/ehaa946.0664 ◽

2020 ◽

Vol 41 (Supplement_2) ◽

Author(s):

F Haertel ◽

S Ijuin ◽

P Lustermann ◽

K Gruen ◽

A Hamadanchi ◽

...

Keyword(s):

Functional Outcome ◽

Left Atrial ◽

Left Atrial Appendage ◽

Tissue Remodeling ◽

Serum Levels ◽

Atrial Appendage ◽

Left Ventricular Ejection ◽

Bleeding Complications ◽

Tenascin C ◽

Galectin 3

Abstract Introduction Left atrial cardiac tissue remodeling following left atrial appendage closure (LAAC) is a scientifically neglected phenomenon until now but might have impact on functional outcome of patients suffering from atrial fibrillation (AF). Thus, our study is focused on quantification of key biomarkers reflecting fibrosis development as a major component within cardiovascular tissue remodeling. Methods Patients (CHA2DS2VASC score ≥1, HASBLED score ≥3) with bleeding complications under anticoagulation therapy and therefore eligible for LAAC were included in the present study. Serum levels of biomarkers of cardiac fibrosis and remodeling (Galectin-3, ST2/IL-2, ST2/IL-1, B domain containing Tenascin-C (B+ Tn-C), C domain containing Tenascin- C (C+ Tn-C)) were determined before device implantation (baseline), 45 days (45d) and 6 months (6M) after LAAC using commercially available ELISAs. To quantify functional outcome, all patients performed a 6-minutes walk test (6- MWT). Transesophageal echocardiography (TEE) was carried out to assess success of the LAAC procedure regarding peri-device leakage (PDL). Results We included 33 patients (age: 73.5±6.7 years; 21 men (64%) and 12 women (36%); BMI: 29.1±5.1 kg/m2; CHA2DS2VASC score: 4.2±1.2; left ventricular ejection fraction: 61.1±9.3%; mean occluder size: 25.9±3.9 mm; type of AF: 46% paroxysmal (15 patients), 55% permanent (18 patients)). Complete LAAC (without any residual low) was achieved in 60% (19 patients) after 45 days and in 87% (29 patients) after 6 months. At baseline, Galectin-3 levels did not show a relevant difference regarding the type of AF (paroxysmal AF: 14.7±5.4 ng/ml vs. permanent AF: 13.1±6.3 ng/ml; p=0.45). We observed a significant increase of serum levels of Galectin-3 [ng/ml] after 45 days vs. baseline (baseline: 13.3±5.8 vs. 45d: 18.3±10.6; p=0.005) with a return to baseline levels after 6 months (baseline: 13.3±5.8 vs. 6M: 12.5±5.4; p=0.28). Compared to patients with successful LAAC, patients with PDL had a trend towards higher levels of Galectin-3 after 6 months (11.3±5.5 ng/ml vs. 16.1±4.1 ng/ml, p=0.09). Measurements of other fibrosis markers were statistically not significantly different. The walking distance measured by the 6-MWT increased significantly from 298.5±89.5 meters at baseline to 335.5±95.1 meters (p=0.04) after 45d and remained significantly elevated after 6M (346.7±122.7 meters; p=0.02). Conclusion The implantation of an LAA occluder device is accompanied by significantly increased circulating levels of the fibrosis biomarker Galectin-3 after 45 days in patients with AF. The regression in serum levels after 6 months probably reflects a successful fibrotic remodeling in the left atrial appendage over time and might be used as surrogate parameter for LAAC success. Increased and stable exercise tolerance after 45 days can be observed. Funding Acknowledgement Type of funding source: None

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Mitochondrial transcription factor A in RORγt+ lymphocytes regulate small intestine homeostasis and metabolism

Nature Communications ◽

10.1038/s41467-021-24755-9 ◽

2021 ◽

Vol 12 (1) ◽

Author(s):

Zheng Fu ◽

Joseph W. Dean ◽

Lifeng Xiong ◽

Michael W. Dougherty ◽

Kristen N. Oliff ◽

...

Keyword(s):

Transcription Factor ◽

Small Intestine ◽

Th17 Cells ◽

Tissue Remodeling ◽

Mitochondrial Transcription ◽

Mitochondrial Transcription Factor ◽

Tuft Cell ◽

Mitochondrial Transcription Factor A

AbstractRORγt+ lymphocytes, including interleukin 17 (IL-17)-producing gamma delta T (γδT17) cells, T helper 17 (Th17) cells, and group 3 innate lymphoid cells (ILC3s), are important immune regulators. Compared to Th17 cells and ILC3s, γδT17 cell metabolism and its role in tissue homeostasis remains poorly understood. Here, we report that the tissue milieu shapes splenic and intestinal γδT17 cell gene signatures. Conditional deletion of mitochondrial transcription factor A (Tfam) in RORγt+ lymphocytes significantly affects systemic γδT17 cell maintenance and reduces ILC3s without affecting Th17 cells in the gut. In vivo deletion of Tfam in RORγt+ lymphocytes, especially in γδT17 cells, results in small intestine tissue remodeling and increases small intestine length by enhancing the type 2 immune responses in mice. Moreover, these mice show dysregulation of the small intestine transcriptome and metabolism with less body weight but enhanced anti-helminth immunity. IL-22, a cytokine produced by RORγt+ lymphocytes inhibits IL-13-induced tuft cell differentiation in vitro, and suppresses the tuft cell-type 2 immune circuit and small intestine lengthening in vivo, highlighting its key role in gut tissue remodeling.

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