Fibrogenesis

Pulmonary fibrosis is an often fatal lung disease. Immune cells such as macrophages were shown to accumulate in the fibrotic lung, but their contribution to the fibrosis development is unclear. To recapitulate the involvement of macrophages in the development of pulmonary fibrosis, we developed a fibrotic microtissue model with cocultured human macrophages and fibroblasts. We show that profibrotic macrophages seeded on topographically controlled stromal tissues became mechanically activated. The resulting co-alignment of macrophages, collagen fibers, and fibroblasts promoted widespread fibrogenesis in micro-engineered lung tissues...

Fibrosis is a progressive pathological process participating in the progression of many diseases and can ultimately result in organ malfunction and failure. Around 45% of deaths in the United States are believed to be attributable to fibrotic disorders, and there are no favorable treatment regiments available to meet the need of blocking fibrogenesis, reversing established fibrosis, and curing diseases, especially in the terminal stage. Therefore, early detection and continuous monitoring provide valuable benefits for patients...

Graves' ophthalmopathy (GO), or thyroid eye disease (TED), is the most frequent extrathyroidal manifestation of Graves' disease (GD). Inflammation and subsequent aberrant tissue remodeling with fibrosis are important pathogenesis. There are many proposed mechanisms and molecular pathways contributing to tissue remodeling and fibrosis in GO, including adipogenesis, fibroblast proliferation and myofibroblasts differentiation, oxidative stress, endoplasmic reticulum (ER) stress, hyaluronan (HA) and glycosaminoglycans (GAGs) accumulation in the extracellular matrix (ECM) and new concepts of epigenetics modification, such as histone modification, DNA methylation, non-coding RNAs, and gut microbiome...

BACKGROUND: Liver cirrhosis leads to portal hypertension (PH) with capillarization of liver sinusoidal endothelial cells (LSECs), although drug treatment options for PH are currently limited. Sodium glucose transporter 2 inhibitors, which are antidiabetic agents, have been shown to improve endothelial dysfunction. We aimed to elucidate the effect of tofogliflozin on PH and liver fibrosis in a rat cirrhosis model. METHODS: Male-F344/NSlc rats repeatedly received carbon tetrachloride (CCl4 ) intraperitoneally to induce PH and liver cirrhosis alongside tofogliflozin (10 or 20 mg/kg)...

Idiopathic pulmonary fibrosis (IPF) is a devastating interstitial lung disease characterized by the relentless deposition of extracellular matrix (ECM), causing lung distortions and dysfunction. Animal models of human IPF can provide great insight into the mechanistic pathways underlying disease progression and a means for evaluating novel therapeutic approaches. In this study, we describe the effect of bleomycin concentration on disease progression in the classical rat bleomycin model. In a dose-response study (1...

Thyroid eye disease (TED) is an autoimmune condition affecting the orbit and the eye with its adnexa, often occurring as an extrathyroidal complication of Graves' disease (GD). Orbital inflammatory infiltration and the stimulation of orbital fibroblasts, triggering de novo adipogenesis, an overproduction of hyaluronan, myofibroblast differentiation, and eventual tissue fibrosis are hallmarks of the disease. Notably, several redox signaling pathways have been shown to intensify inflammation and to promote adipogenesis, myofibroblast differentiation, and fibrogenesis by upregulating potent cytokines, such as interleukin (IL)-1β, IL-6, and transforming growth factor (TGF)-β...

Pancreatic cancer is characterized by a densely fibrotic stroma. The fibrotic stroma hinders the intratumoral penetration of nanomedicine and diminishes therapeutic efficacy. Fibrosis is characterized by an abnormal organization of extracellular matrix (ECM) components, namely the abnormal deposition and/or orientation of collagen and fibronectin. Abnormal ECM organization is chiefly driven by pathological signaling in pancreatic stellate cells (PSCs), the main cell type involved in fibrogenesis. However, whether targeting signaling pathways involved in abnormal ECM organization improves the intratumoral penetration of nanomedicines is unknown...

Epigenetic regulations, including DNA methylation, are critical to the development and progression of kidney fibrosis, but the underlying mechanisms remain elusive. Here, we show that fibrosis of the mouse kidney was associated with the induction of DNA methyltransferases and increases in global DNA methylation and was alleviated by the DNA methyltransferase inhibitor 5-Aza-2'-deoxycytidine (5-Aza). Genome wide analysis demonstrated the hypermethylation of 94 genes in mouse unilateral ureteral obstruction kidneys, which was markedly reduced by 5-Aza...

Phosphodiesterase 4 (PDE4), crucial in regulating the cyclic adenosine monophosphate (cAMP) signaling pathway, significantly impacts liver pathophysiology. This article highlights the comprehensive effects of PDE4 on liver health and disease, and its potential as a therapeutic agent. PDE4's role in degrading cAMP disrupts intracellular signaling, increasing pro-inflammatory cytokines like tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6). This contributes to liver inflammation in conditions such as hepatitis and non-alcoholic steatohepatitis (NASH)...

Fibrosis is primarily described as the deposition of excessive extracellular matrix, but in many tissues it also involves a loss of lipid or lipid-filled cells. Lipid-filled cells are critical to tissue function and integrity in many tissues including the skin and lungs. Thus, loss or depletion of lipid-filled cells during fibrogenesis, has implications for tissue function. In some contexts, lipid-filled cells can impact ECM composition and stability, highlighting their importance in fibrotic transformation...

Pulmonary Fibrosis (PF) is a fatal lung disease with complicated pathogenesis. Astragaloside IV (ASV) has been discovered to alleviate PF progression, and the potential molecular mechanism of ASV in the development of PF need to be further clarified. Bleomycin (BLM) was used to construct PF in vivo model. Expression levels of circ_0008898, miR-211-5p, high mobility group protein B1 (HMGB1), alpha smooth muscle Actin (α-SMA) and Collagen I were examined by Quantitative real time polymerase chain reaction (qRT-PCR) and western blot...

Cardiac fibrosis, associated with right heart dysfunction, results in significant morbidity and mortality. Stimulated by various cellular and humoral stimuli, cardiac fibroblasts, macrophages, CD4+ and CD8+ T cells, mast and endothelial cells promote fibrogenesis directly and indirectly by synthesizing numerous profibrotic factors. Several systems, including the transforming growth factor-beta and the renin-angiotensin system, produce type I and III collagen, fibronectin and α-smooth muscle actin, thus modifying the extracellular matrix...

Environmental tobacco smoke (ETS) is known to cause lung inflammatory and injurious responses. Smoke exposure is associated with the pathobiology related to lung fibrosis, whereas the mechanism that ETS exposure augments pulmonary fibrogenesis is unclear. We hypothesized that ETS exposure could exacerbate fibrotic responses via collagen dynamic dysregulation and complement activation. C57BL/6J and p16-3MR mice were exposed to ETS followed by bleomycin administration. ETS exposure exacerbated bleomycin-induced collagen and lysyl oxidase overexpression in the fibrotic lesion...

Endometrial fibrosis leads to the destruction of endometrial function and affects reproductive performance. However, mechanisms underlying the development of endometrial fibrosis in sheep remain unclear. We use transcriptomic, proteomic, and metabolomic studies to reveal the formation mechanisms of endometrial fibrosis. The results showed that the fibrotic endometrial tissue phenotype presented fewer glands, accompanied by collagen deposition. Transcriptomic results indicated alterations in genes associated with the synthesis and degradation of extracellular matrix components, which alter metabolite homeostasis, especially in glycerophospholipid metabolism...

Cardiac fibrosis is a serious health problem because it is a common pathological change in almost all forms of cardiovascular diseases. Cardiac fibrosis is characterized by the transdifferentiation of cardiac fibroblasts (CFs) into cardiac myofibroblasts and the excessive deposition of extracellular matrix (ECM) components produced by activated myofibroblasts, which leads to fibrotic scar formation and subsequent cardiac dysfunction. However, there are currently few effective therapeutic strategies protecting against fibrogenesis...

BACKGROUND: Hepatic fibrosis, a common pathological process that occurs in end-stage liver diseases, is a serious public health problem and lacks effective therapy. Notoginsenoside R1 (NR1) is a small molecule derived from the traditional Chinese medicine Sanqi, exhibiting great potential in treating diverse metabolie disorders. Here we aimed to enquired the role of NR1 in liver fibrosis and its underlying mechanism in hepatoprotective effects. METHODS: We investigated the anti-fibrosis effects of NR1 using CCl4 -induced mouse mode of liver fibrosis as well as TGF-β1-activated JS-1, LX-2 cells and primary hepatic stellate cells...

Aryl hydrocarbon receptor (AhR) was originally identified as an environmental sensor that responds to pollutants. Subsequent research has revealed that AhR recognizes multiple exogenous and endogenous molecules, including uremic toxins retained in the body due to the decline in renal function. Therefore, AhR is also considered to be a uremic toxin receptor. As a ligand-activated transcriptional factor, the activation of AhR is involved in cell differentiation and senescence, lipid metabolism and fibrogenesis...

BACKGROUND: The alleviating effect of paeoniflorin (Pae) on liver fibrosis has been established; however, the molecular mechanism and specific target(s) underlying this effect remain elusive. PURPOSE: This study was to investigate the molecular mechanism underlying the regulatory effect of Pae on hepatic stellate cells (HSCs) activation in liver fibrosis, with a specific focus on the role of Pae in modulating histone methylation modifications. METHODS: The therapeutic effect of Pae was evaluated by establishing in vivo and in vitro models of carbon tetrachloride (CCl4 )-induced mice and transforming growth factor β1 (TGF-β1 )-induced LX-2 cells, respectively...

BACKGROUND: Jaceosidin (JA) is a natural flavone extracted from Artemisia that is used as a food and traditional medicinal herb. It has been reported to possess numerous biological activities. However, the regulatory mechanisms underlying amelioration of hepatic fibrosis remain unclear. HYPOTHESIS/PURPOSE: We hypothesized that jaceosidin acid (JA) modulates hepatic fibrosis and inflammation. METHODS: Thioacetamide (TAA) was used to establish an HF mouse model...

Liver fibrosis, characterized by scar tissue formation, can ultimately result in liver failure. It's a major cause of morbidity and mortality globally, often associated with chronic liver diseases like hepatitis or alcoholic and non-alcoholic fatty liver diseases. However, current treatment options are limited, highlighting the urgent need for the development of new therapies. As a reversible regulatory mechanism, epigenetic modification is implicated in many biological processes, including liver fibrosis. Exploring the epigenetic mechanisms involved in liver fibrosis could provide valuable insights into developing new treatments for chronic liver diseases, although the current evidence is still controversial...