【摘 要】
：
Idiopathic pulmonary fibrosis (IPF) is an aging-associated disease with a poor prognosis.Emerging evidence has revealed that targeting senescent cells may be a potential treatment for IPF.In this study,we aimed to explore whether roxithromycin (RXM) can i
【机 构】
：
State Key Laboratory of Drug Research,Shanghai Institute of Materia Medica,Chinese Academy of Scienc
论文部分内容阅读
Idiopathic pulmonary fibrosis (IPF) is an aging-associated disease with a poor prognosis.Emerging evidence has revealed that targeting senescent cells may be a potential treatment for IPF.In this study,we aimed to explore whether roxithromycin (RXM) can improve lung fibrosis by targeting senescent cells.First,we confirmed the ability of RXM to selectively kill senescent cells by inducing apoptosis and inhibiting the expression of senescence-associated secretory phenotype (SASP) factors,suggesting the potential role of RXM as a “senolytic” and “senomorphic” drug.Next,we observed that TGF-β-and senescent cell-induced lung fibroblast activation was inhibited by RXM treatment,which prompted us to further investigate its effect in vivo.In a mouse model of bleomycin (BLM)-induced pulmonary fibrosis,RXM was shown to attenuate lung injury,inflammation,and fibrosis.Furthermore,the senescent phenotype of lung tissues induced by BLM was significantly diminished after RXM administration,indicating the potential of RXM as an antifibrotic and antisenescent agent.Interestingly,NADPH oxidase 4 (NOX4),implicated in lung fibrosis and cell senescence,was shown to be inhibited by RXM treatments.The antifibroblast activation and antisenescent effects of RXM were abolished in NOX4 knockdown cells,demonstrating that RXM may ameliorate BLM-induced pulmonary fibrosis by targeting senescent cells mediated by the NOX4 pathway.Collectively,these data demonstrated that RXM may be a potential clinical agent for IPF and further supported the notion that targeting cellular senescence is a promising treatment for progressive age-related disease.
其他文献
Proliferation of vascular smooth muscle cells (VSMCs) greatly contributes to vascular remodeling in hypertension.This study is to determine the roles and mechanisms of miR-135a-5p intervention in attenuating VSMC proliferation and vascular remodeling in s
Accumulating evidence shows that agents targeting gut dysbiosis are effective for improving symptoms of irritable bowel syndrome (IBS).However,the potential mechanisms remain unclear.In this study we investigated the effects of berberine on the microbiota
Caffeine induces multiple vascular effects.In this study we investigated the angiogenic effect of physiological concentrations of caffeine with focus on endothelial cell behaviors (migration and proliferation) during angiogenesis and its mitochondrial and
Macrophage-mediated inflammation plays an important role in hypertensive cardiac remodeling,whereas effective pharmacological treatments targeting cardiac inflammation remain unclear.Lipoprotein-associated phospholipase A2 (Lp-PLA2)contributes to vascular
NOD-like receptor (NLR) family pyrin domain-containing-3 (NLRP3) inflammasome is implicated in inflammation-associated diseases such as multiple sclerosis,Parkinson\'s disease,and stroke.Targeting the NLRP3 inflammasome is beneficial to these diseases,b
RAS-driven colorectal cancer relies on glucose metabolism to support uncontrolled growth.However,monotherapy with glycolysis inhibitors like 2-deoxy-D-glucose causes limited effectiveness.Recent studies suggest that anti-tumor effects of glycolysis inhibi
Nuclear factor kappa B (NF-κB) activation contributes to many vascular inflammatory diseases.The present study tested the hypothesis that microRNA-17-3p (miR-17-3p) suppresses the pro-inflammatory responses via NF-κB signaling in vascular endothelium.Huma
Pre-B-cell leukemia transcription factor 3 (PBX3) is a member of the PBX family and contains a highly conserved homologous domain.PBX3 is involved in the progression of gastric cancer,colorectal cancer,and prostate cancer;however,the detailed mechanism by
Glioblastoma multiforme (GBM) is the most common and malignant type of primary brain tumor,and 95％ of patients die within 2 years after diagnosis.In this study,aiming to overcome chemoresistance to the first-line drug temozolomide (TMZ),we carried out res
Metastasis is the main cause of mortality in patients with cancer.Epithelial-mesenchymal transition (EMT),a crucial process in cancer metastasis,is an established target for antimetastatic drug development.LFG-500,a novel synthetic flavonoid,has been reve