CD206 and dust particles are prognostic biomarkers of progressive fibrosing interstitial lung disease associated with air pollutant exposureKadushkin, Yudina, Lukashevich
et alSci Rep (2025) 15 (1), 9669
Abstract: Current management strategies for progressive fibrosing interstitial lung disease (PF-ILD) and non-PF-ILD differ significantly, underscoring the need for early identification of PF-ILD patients. We analyzed the expression of macrophage markers and the number of dust particles (DP) in lung tissue, as well as complete blood count and blood chemistry tests to identify biomarkers of PF-ILD, and examined the effect of certain pollutants on these biomarkers. Lung biopsies were collected from 73 non-PF-ILD patients and 36 PF-ILD patients. DP were quantified in alveolar wall cells (DP-aw) and desquamated epithelial cells (DP-desq) using polarizing light microscopy. Expression of CD206, transforming growth factor β1 (TGF-β1), connective tissue growth factor (CTGF), C-X-C motif ligand 13 (CXCL13), fibroblast growth factor 2 (FGF-2), tumor necrosis factor α (TNFα), and interleukin 1β (IL-1β) was assessed in lung tissue by immunohistochemistry. The numbers of DP-desq, pulmonary expression of CXCL13, IL-1β and CD206 were higher in ILD patients resided for ≥ 15 days per year in places with 24-hour ambient PM10 level of ≥ 50 µg/m3 compared with ILD patients exposed for < 15 days per year to the similar PM10 concentration. Additionally, CXCL13 expression in lung tissue was higher in smoking ILD patients than in non-smoking ILD patients. Compared with non-PF-ILD patients, PF-ILD patients exhibited higher numbers of DP-aw and DP-desq, as well as increased expression of CD206, CXCL13, IL-1β, TGF-β1, and CTGF in lung tissue. Elevated blood neutrophil-to-lymphocyte (NLR) and platelet-to-lymphocyte ratios were also observed in PF-ILD patients. These biomarkers were found to be independent predictors of PF-ILD. A regression logistic model incorporating NLR, CD206, and DP-desq predicted PF-ILD with an AUC of 0.847, sensitivity of 84.6%, and specificity of 83.3%. Our findings may be useful in predicting PF-ILD and highlight the need for reducing pollutant emission.© 2025. The Author(s).
TLR2 activates AP-1 to facilitate CTGF transcription and stimulate doxorubicin-induced myocardial injuryHong, Cai, Zhan
et alBr J Pharmacol (2025)
Abstract: Our study aimed to explore the mechanistic network of toll-like receptor 2 (TLR2)/activator protein-1 (AP-1) combined with SOX10 activation of the mitogen-activated protein kinase (MAPK) pathway via connective tissue growth factor (CTGF) in doxorubicin (Dox)-induced myocardial injury.Rats with Dox-induced myocardial injury were treated with a TLR2 inhibitor or CTGF silencing lentiviral vector. H9c2 cells were treated with genetic vectors or MAPK pathway activators. Cardiac function was tested using echocardiography and serum markers. H&E, Sirius red and TUNEL staining were used to detect myocardial pathological changes, collagen accumulation and apoptosis. Western blot was used to detect proteins related to cardiac hypertrophy, fibrosis, apoptosis and the MAPK pathway. H9c2 cell injury was assessed by testing cell viability, lactate dehydrogenase (LDH) release and mitochondrial membrane potential.TLR2 and CTGF were highly expressed in patients with heart failure, and Dox treatment further increased their expression. Inhibiting TLR2 or silencing CTGF improved cardiac function and reduced myocardial fibrosis and apoptosis in Dox-treated rats. Silencing of TLR2 alleviated Dox-induced H9c2 cell injury, which was nullified by CTGF overexpression. TLR2 activated AP-1, which cooperated with SOX10 to promote CTGF transcription. MAPK activation aggravated H9c2 cells against Dox-induced injury.TLR2 activates AP-1 which cooperates with SOX10 to promote CTGF transcription and subsequently activate the MAPK pathway, thereby stimulating Dox-induced myocardial injury.© 2025 British Pharmacological Society.
Specific functional connectivity of molecular subtypes of subplate and layer 6b neuronsChang, Xu, Nehs
et alJ Neurosci (2025)
Abstract: Subplate neurons (SpNs) are among the earliest generated cortical neurons that form functional cortical synapses, and aid in cortical circuit development. A fraction of SpNs survive and form layer 6b in the adult cortex. While SpNs exhibit a large variety of molecular identities, it is unclear if molecular identity correlates with functional or connectomic identities and if different SpNs have similar developmental trajectories. To resolve these questions, we here characterize the functional intracortical circuits to molecularly identified subpopulations of SpNs with SpN-specific Cre-lines (CTGF-dgCre and Drd1-Cre) in in vitro brain slices of the primary auditory cortex using whole-cell patch clamp recordings and laser-scanning photostimulation. We targeted three age groups: before (postnatal day (P)7-P9) and after (P14-P20) the ear canal opens and when circuits are mature (P60-P80). The excitatory intracortical circuits impinging on both subtypes revealed similar patterns, but not the inhibitory circuits, particularly those from subplate/layer 6b. At P7-P9, Drd1 neurons received stronger inhibition from the subplate compared to CTGF neurons. The functional circuits on SpNs prune with age. By P60-P80, the inhibitory connections from layer 6b on CTGF neurons increased and became significantly abundant than those on Drd1 neurons. However, the inhibition strength between the two subtypes remained unchanged, suggesting that inhibition on CTGF was generally weaker at each stimulation site. Thus, SpNs exhibit diverse neuronal morphologies and intracortical input patterns, independent of molecular expression. Thus, although the subplate comprises distinct molecular classes of neurons, their molecular expression is not clearly correlated with morphologies and functional circuits throughout development.Significance statement Subplate neurons pioneer cortical circuit formation and shape its maturation. Subplate neurons can be categorized into different subpopulation based on their molecular identities. However, the relationship between functional circuitry and molecular identities was unclear. Our study demonstrated that excitatory inputs on different molecular classes of subplate neurons develop similarly but not the inhibitory inputs, particularly those from within subplate/layer6b. Moreover, subplate neurons within the same molecular classes exhibit diverse patterns of intracortical circuit connections and neuronal morphologies. This diversity becomes more pronounced in adulthood. Therefore, distinguishing the functional connectivity between the two subtypes based solely on their molecular identities is impossible. Overall, the molecular expression of subplate neurons is not clearly correlated with their morphologies and functional connectivity pattern.Copyright © 2025 the authors.
Fibrosis factor CTGF facilitates VCAM‑1‑dependent monocyte adhesion to osteoarthritis synovial fibroblasts via the FAK and JNK pathwaysLiu, Law, Wu
et alMol Med Rep (2025) 31 (5)
Abstract: Osteoarthritis (OA) is a long‑term, degenerative joint disease that presents significant clinical challenges and imposes considerable financial burdens. Fibrosis is closely intertwined with the pathogenesis of various degenerative diseases, including OA. Using data from the GDS5401 dataset, the present study determined that expression levels of the fibrosis factor connective tissue growth factor (CTGF) were significantly higher in OA patients than in normal individuals. The present study also identified CTGF elevated expression levels in both OA patients compared with healthy controls and in rats with anterior cruciate ligament transection‑induced OA versus controls. Stimulating OA synovial fibroblasts (OASFs) with CTGF was shown to promote vascular cell adhesion molecule‑1 (VCAM‑1) production, thereby facilitating monocyte adhesion to OASFs. Analysis of a large dataset revealed that monocytes are the only mononuclear cells with significantly elevated levels in OA patients. It also appeared that CTGF‑induced VCAM‑1 production and monocyte adhesion were mediated via the focal adhesion kinase and JNK pathways. These findings suggest that CTGF contributes to OA progression by enhancing monocyte adhesion to the synovial membrane.
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