macrophage fibrosis

Excessive extracellular matrix (ECM) deposition is a defining feature of cardiac fibrosis. Most notably, it is characterized by a significant change in the concentration and volume fraction of collagen I, a disproportionate deposition of collagen subtypes, and a disturbed ECM network arrangement, which directly affect the systolic and diastolic functions of the heart. Immune cells that reside within or infiltrate the myocardium, including macrophages, play important roles in fibroblast activation and consequent ECM remodeling...

BACKGROUND: Fibrosis results from excessive scar formation after tissue injury. Injured cells release alarmins such as interleukin 1 (IL-1) α and β as primary mediators initiating tissue repair. However, how alarmins from different cell types differentially regulate fibrosis remains to be explored. METHODS: Here, we used tissue specific knockout strategy to illustrate a unique contribution of endothelial cell-derived IL-1α to lung and liver fibrosis...

Liver fibrosis is a coordinated response to tissue injury that is mediated by immune cell interactions. A mitochondria-regulated information-processing (MIP) nanosystem that promotes immune cell communication and interactions to inhibit liver fibrosis is designed. The MIP nanosystem mimics the alkaline amino acid domain of mitochondrial precursor proteins, providing precise targeting of the mitochondria. The MIP nanosystem is driven by light to modulate the mitochondria of hepatic stellate cells, resulting in the release of mitochondrial DNA into the fibrotic microenvironment, as detected by macrophages...

The improvement of the myocardial microenvironment largely determines the prognosis of myocardial infarction (MI). After MI, early removal of excessive reactive oxygen species (ROS) in the microenvironment can alleviate oxidative stress injury and promote M2 phenotype polarization of macrophages, which is important for advocating myocardial repair. In this study, we combined traditional natural hydrogel materials chitosan (CS) and gelatin (Gel) to encapsulate polydopamine-modified black phosphorus nanosheets (BP@PDA)...

OBJECTIVES: This study investigates the role of TNF-induced protein 3 (TNFAIP3) and CCAAT/enhancer-binding protein β (C/EBPβ) in alveolar macrophages (AMs) of patients with systemic sclerosis-associated interstitial lung disease (SSc-ILD) and their influence on pulmonary fibrosis. METHODS: Transfection of HEK293T cells and AMs with plasmids carrying TNFAIP3 and C/EBPβ was performed, followed by co-culturing AMs with pulmonary fibroblasts. Immunoblotting analysis was then utilized to assess the expression of TNFAIP3, C/EBPβ, and collagen type 1 (Col1)...

BACKGROUND: The association between tuberculous fibrosis and lung cancer development has been reported by some epidemiological and experimental studies; however, its underlying mechanisms remain unclear, and the role of macrophage (MФ) polarization in cancer progression is unknown. The aim of the present study was to investigate the role of M2 Arg-1+ MФ in tuberculous pleurisy-assisted tumorigenicity in vitro and in vivo. METHODS: The interactions between tuberculous pleural effusion (TPE)-induced M2 Arg-1+ MФ and A549 lung cancer cells were evaluated...

Idiopathic pulmonary fibrosis (IPF) is a debilitating, life-threatening irreversible lung disease characterized by the excessive accumulation of fibrotic tissue in the lungs, impairing their function. The exact mechanisms underlying Pulmonary fibrosis (PF) are multifaceted and not yet fully understood. Reports show that during COVID-19 pandemic, PF was dramatically increased due to the hyperactivation of the immune system. Neutrophils and macrophages are the patrolling immune cells that keep the microenvironment balanced...

IgA nephropathy (IgAN) represents the main cause of renal failure, while the precise pathogenetic mechanisms have not been fully determined. Herein, we conducted a cross-species single-cell survey on human IgAN and mouse and rat IgAN models to explore the pathogenic programs. Cross-species single-cell RNA sequencing (scRNA-Seq) revealed that the IgAN mesangial cells (MCs) expressed high levels of inflammatory signatures CXCL12, CCL2, CSF1, and IL-34 and specifically interacted with IgAN macrophages via the CXCL12/CXCR4, CSF1/IL-34/CSF1 receptor, and integrin subunit alpha X/integrin subunit alpha M/complement C3 (C3) axes...

Chronic inflammation is a key element in the progression of essential hypertension (EH). Calcium plays a key role in inflammation, so its receptor, the calcium-sensing receptor (CaSR), is an essential mediator of the inflammatory process. Compelling evidence suggests that CaSR mediates inflammation in tissues and immune cells, where it mediates their activity and chemotaxis. Macrophages (Mφs) play a major role in the inflammatory response process. This study provided convincing evidence that R568, a positive regulator of CaSR, was effective in lowering blood pressure in spontaneously hypertensive rats (SHRs), improving cardiac function by alleviating cardiac hypertrophy and fibrosis...

Tendon adhesion is a common complication after tendon injury with the development of accumulated fibrotic tissues without effective anti-fibrotic therapies, resulting in severe disability. Macrophages are widely recognized as a fibrotic trigger during peritendinous adhesion formation. However, different clusters of macrophages have various functions and receive multiple regulation, which are both still unknown. In our current study, multi-omics analysis including single-cell RNA sequencing and proteomics was performed on both human and mouse tendon adhesion tissue at different stages after tendon injury...

Interleukin-1β (IL-1β) contributes to interstitial lung disease (ILD) and pulmonary fibrosis (PF), thus representing a potential therapeutic target for PF. In this study, we first verified the increased expression of IL-1β in human fibrotic lung specimens and mouse lung tissues after intratracheal (i.t.) instillation of bleomycin (BLM), after which the pro-inflammatory and pro-fibrotic effects of recombinant IL-1β were tested in mice. The results above suggested that vaccination against IL-1β could be an effective strategy for managing PF...

BACKGROUND: Inflammation is pathogenically implicated in pulmonary arterial hypertension; however, it has not been adequately targeted therapeutically. We investigated whether neuromodulation of an anti-inflammatory neuroimmune pathway involving the splenic nerve using noninvasive, focused ultrasound stimulation of the spleen (sFUS) can improve experimental pulmonary hypertension. METHODS: Pulmonary hypertension was induced in rats either by Sugen 5416 (20 mg/kg SQ) injection, followed by 21 (or 35) days of hypoxia (sugen/hypoxia model), or by monocrotaline (60 mg/kg IP) injection (monocrotaline model)...

BACKGROUND AND AIMS: Recent studies have highlighted the beneficial effect of resolvin D1 (RvD1), a DHA-derived specialized pro-resolving mediator, on metabolic dysfunction-associated steatohepatitis (MASH), but the underlying mechanisms are not well understood. Our study aims to determine the mechanism by which RvD1 protects against MASH progression. METHODS: RvD1 was administered to mice with experimental MASH, followed by bulk and single-cell RNA sequencing analysis...

BACKGROUND: Liver fibrosis typically develops as a result of chronic liver injury, which involves inflammatory and regenerative processes. The triggering receptor expressed on myeloid cells 2 (TREM2), predominantly expressing in hepatic non-parenchymal cells, plays a crucial role in regulating the function of macrophages. However, its mechanism in liver fibrosis remains poorly defined. METHODS: Experimental liver fibrosis models in wild type and TREM2-/- mice, and in vitro studies with AML-12 cells and Raw264...

OBJECTIVE: To investigate the protective effect of arbutin against CCl4 -induced hepatic fibrosis in mice and explore the underlying mechanisms. METHODS: Twenty-four C57BL/6 mice were randomly divided into control group, model group, and low- and high-dose arbutin treatment (25 and 50 mg/kg, respectively) groups. Mouse models of liver fibrosis were established by intraperitoneal injection of CCl4 , and arbutin was administered daily via gavage for 6 weeks. After the treatments, serum biochemical parameters of the mice were tested, and liver tissues were taken for HE staining, Sirius Red staining and immunohistochemical staining...

OBJECTIVE: To observe the effect of Shenqi Chongcao (SQCC) Formula on the ASS1/src/STAT3 signaling pathway in a rat model of lung fibrosis and explore its therapeutic mechanism. METHODS: A total of 120 male SD rats were divided equally into 5 groups, including a blank control group with saline treatment and 4 groups of rat models of idiopathic pulmonary fibrosis induced by intratracheal instillation of bleomycin. One day after modeling, the rat models were treated with daily gavage of 10 mL/kg saline, SQCC decoction (0...

A subgroup of schizophrenia cases with elevated inflammation have reduced neurogenesis markers and increased macrophage density in the human subependymal zone (SEZ; also termed subventricular zone or SVZ) neurogenic niche. Inflammation can impair neurogenesis; however, it is unclear which other pathways are associated with reduced neurogenesis. This research aimed to discover transcriptomic differences between inflammatory subgroups of schizophrenia in the SEZ. Total RNA sequencing was performed on SEZ tissue from schizophrenia cases, designated into low inflammation (n = 13) and high inflammation (n = 14) subgroups, based on cluster analysis of inflammation marker gene expression...

Epithelial-mesenchymal transition (EMT) plays a crucial role in regulating inflammatory responses and fibrosis formation. This study aims to explore the molecular mechanisms of EMT-related genes in Crohn's disease (CD) through bioinformatics methods and identify potential key biomarkers. In our research, we identified differentially expressed genes (DEGs) related to EMT based on the GSE52746 dataset and the gene set in the GeneCards database. Key genes were identified through Lasso-cox and Random Forest and validated using the external dataset GSE10616...

BACKGROUND: Human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) have demonstrated efficacy in repairing uterine scars, although the underlying mechanisms remain unclear. METHODS: Uterine injury was surgically induced in a rat model, followed by immediate transplantation of 5 × 10 ^ 5 hUC-MSCs to each side of the uterus. Uterine morphology was evaluated at days 14 and 30 using HE and Masson staining. Immunohistochemistry assessed macrophage polarization, angiogenesis and endometrial receptivity in the endometrium...

BACKGROUND: Systemic sclerosis (SSc) is an autoimmune disease characterized by vascular injury and inflammation, followed by excessive fibrosis of the skin and other internal organs, including the lungs. CX3CL1 (fractalkine), a chemokine expressed on endothelial cells, supports the migration of macrophages and T cells that express its specific receptor CX3CR1 into targeted tissues. We previously reported that anti-CX3CL1 monoclonal antibody (mAb) treatment significantly inhibited transforming growth factor (TGF)-β1-induced expression of type I collagen and fibronectin 1 in human dermal fibroblasts...