Pulmonary artery adventitial fibroblasts, the most abundant cellular constituent of adventitia, are often the first to be activated and reprogrammed to then influence the tone and structure of the vessel wall in pulmonary arterial hypertension (PAH). Our previous study found that interruption of CD40 ligand (CD40L)-CD40 signaling improves the efficacy of transplanted endothelial progenitor cells in monocrotaline induced-PAH. However, whether CD40L-CD40 signaling is involved in the activation of adventitial fibroblasts in PAH and whether Drosophila behavior human splicing (DBHS) protein family members have any roles during adventitial fibroblasts activation are completely unclear. Here, we show that soluble CD40L (sCD40L) stimulation progressively increases pro-inflammatory activity, proliferation, and migration of pulmonary adventitial fibroblasts. Besides, sCD40L stimulation decreases splicing factor proline- and glutamine-rich protein (SFPQ) protein (one member of DBHS protein family) expression, while SFPQ overexpression suppresses sCD40L stimulation-induced proliferation and migration of pulmonary adventitial fibroblasts by repressing CD40 transcription. Moreover, ChIP assays found that sCD40L stimulation promotes histone H3 tri-methylation at lysine 4 (H3K4me3), H3K36me3, and H3K27 acetylation (H3K27ac) modifications on CD40 promoter region in pulmonary adventitial fibroblasts, while SFPQ overexpression decreases H3K36me3 modification and increases H3K36ac on CD40 promoter region by interacting with histone deacetylase-1 (HDAC1) to inhibit CD40 transcription. This in-depth study shows that CD40L-CD40 signaling promotes activation of pulmonary adventitial fibroblasts by increasing proliferation, migration, and pro-inflammatory activity of adventitial fibroblasts, and SFPQ could inhibit CD40 transcription though switching H3K36me3 to H3K36ac modifications on its promoter by interacting with HDAC1. This study, first, uncovers the roles of SFPQ on CD40L-CD40 signaling-mediated activation of pulmonary adventitial fibroblasts.
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http://dx.doi.org/10.1002/cbin.11216 | DOI Listing |
JCI Insight
January 2025
Department of Otolaryngology, Nationwide Children's Hospital, Columbus, United States of America.
Surgery of the tracheobronchial tree carries high morbidity, with over half of the complications occurring at the anastomosis. Although fibroblasts are crucial in airway wound healing, the underlying cellular and molecular mechanisms in airway reconstruction remain unknown. We hypothesized that airway reconstruction initiates a surgery-induced stress (SIS) response, altering fibroblast communication within airway tissues.
View Article and Find Full Text PDFJ Ethnopharmacol
January 2025
School of Integrated Traditional Chinese and Western Medicine, Hunan University of Chinese Medicine, 300 Bachelor Road, Hanpu Science and Education Park, Yuelu District, 410208Changsha City, Hunan Province, China; Hunan Key Laboratory of Integrated Chinese and Western Medicine for Prevention and Treatment of Heart and Brain Diseases, 410208, Changsha, China. Electronic address:
Ethnopharmacological Relevance: Astragali Radix-Angelicae Sinensis Radix is an important traditional Chinese medicine used for the treatment of cardiovascular diseases. Our previous studies have shown that Astragali Radix-Angelicae Sinensis Radix can inhibit vascular intimal hyperplasia and improve the blood vessel wall's ECM deposition, among which six main active components can be absorbed into the blood, suggesting that these components may be the main pharmacodynamic substances of Astragali Radix-Angelicae Sinensis Radix against vascular intimal hyperplasia.
Aim Of The Study: A mouse model of atherosclerosis was used to study the relationship between the anti-intimal hyperplasia effect of Astragali Radix-Angelicae Sinensis Radix and the inhibition of VAF activation and ECM synthesis.
Life Sci
January 2025
Department of Pharmacy, Xinhua Hospital Affiliated to Shanghai Jiaotong University School of Medicine, Shanghai 200092, China. Electronic address:
Pathological vascular remodeling (VR) is characterized by structural and functional alterations in the vascular wall resulting from injury, which significantly contribute to the development of cardiovascular diseases (CVDs). The vascular wall consists primarily of endothelial cells (ECs), vascular smooth muscle cells (VSMCs), and adventitial fibroblasts (AFs), whose interactions are crucial for both the formation of the vascular system and the maintenance of mature blood vessels. Disruptions in the communication between these cell types have been implicated in the progression of VR.
View Article and Find Full Text PDFInt J Mol Sci
November 2024
Department of Respirology, Graduate School of Medicine, Chiba University, Chiba 260-8670, Japan.
In hypoxic pulmonary hypertension (PH), pulmonary vascular remodeling is characterized by the emergence of activated adventitial fibroblasts, leading to medial smooth muscle hyperplasia. Previous studies have suggested that CD26/dipeptidyl peptidase-4 (DPP4) plays a crucial role in the pathobiological processes in lung diseases. However, its role in pulmonary fibroblasts in hypoxic PH remains unknown.
View Article and Find Full Text PDFPhysiol Res
November 2024
Institute of Physiology of the Czech Academy of Sciences, Prague, Czech Republic.
Pulmonary hypertension is a complex and heterogeneous condition with five main subtypes (groups). This review focuses on pulmonary hypertension caused by chronic hypoxia (hypoxic pulmonary hypertension, HPH, group 3). It is based mainly on our own experimental work, especially our collaboration with the group of Professor Herget, whose fifth anniversary of death we commemorate.
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