microRNAs (miRNAs) derived from viruses, have been detected in body fluids and are known to regulate the expression of host genes. Recent evidence indicates that SARS-CoV-2-encoded miRNAs could contribute to pulmonary...microRNAs (miRNAs) derived from viruses, have been detected in body fluids and are known to regulate the expression of host genes. Recent evidence indicates that SARS-CoV-2-encoded miRNAs could contribute to pulmonary disease. Pulmonary fibrosis is an important complication in SARS-CoV-2 infected patients, either during hospitalization or after discharge, however, the underlying mechanisms are not fully elucidated. Here, we report a SARS-CoV-2-encoded miRNA, miR-nsp3-3p, facilitates host pulmonary fibrosis by inhibiting expression of activated leukocyte cell adhesion molecule (ALCAM) and promoting epithelial-mesenchymal transition (EMT). First, we detected miR-nsp3-3p in clinical specimens and found it was remarkably increased in throat swabs and alveolar lavage fluids from severe/critical COVID-19 patients compared to control groups or mild/moderate patients. We further revealed that adeno-associated virus (AAV)-nsp3 infection can induce pulmonary fibrosis in BALB/c mice while miR-nsp3-3p antagomirs can reverse that, and ALCAM was found to be as a target gene of miR-nsp3-3p. miR-nsp3-3p overexpression can inhibit the expression of ALCAM and promote EMT of pulmonary epithelial cells. Moreover, overexpression of ALCAM can reverse the miR-nsp3-3p-induced EMT and fibrosis. These findings highlight the essential role of SARS-CoV-2-encoded miRNAs in promoting the pathological progression of lung disease, and provide novel insights into the interactions between viral miRNAs and host pathology.展开更多
During development and regeneration,axonal growth depends on a rapid response to extracellular growth and guidance molecules.One mechanism underlying this rapid response is local protein synthesis（Jung et al.,2012）....During development and regeneration,axonal growth depends on a rapid response to extracellular growth and guidance molecules.One mechanism underlying this rapid response is local protein synthesis（Jung et al.,2012）.Local protein synthesis is a highly tuned,展开更多
Psoriasis is a chronic inflammatory skin disease with a strong genetic background and is triggered by environmental factors.Available evidence supports CD6,a lymphocyte surface receptor mostly expressed by T cells,as ...Psoriasis is a chronic inflammatory skin disease with a strong genetic background and is triggered by environmental factors.Available evidence supports CD6,a lymphocyte surface receptor mostly expressed by T cells,as a putative target in autoimmunity.Accordingly,a humanized anti-CD6 antibody has been assayed for the treatment of certain autoimmune disorders,including psoriasis.Here,we present novel evidence in mice and humans for a direct involvement of CD6 in psoriasis pathophysiology.First,an attenuated form of imiquimod-induced psoriasis-like skin inflammation was demonstrated in CD6-deficient mice,as deduced from lower epidermal thickness and local reduced production of pro-inflammatory cytokines,namely,interleukin-17A.Thus,isolated CD4+CD62L+T cells from CD6-deficient mice displayed decreased in vitro T-helper type 17 polarization.Second,a statistically significant association between CD6 single-nucleotide polymorphisms(rs17824933,rs11230563 and rs12360861)and more severe forms of psoriasis was demonstrated in a cohort of 304 patients at three public hospitals from the metropolitan area of Barcelona.Taken together,these results provide new supportive evidence of the contribution of the CD6 lymphocyte receptor in psoriasis at both experimental and clinical levels.展开更多
基金supported by the National Natural Science Foundations of China(82372342)the Clinical Diagnosis and Treatment New Technology Project of Jinling Hospital(No.22LCZLXJS40).
文摘microRNAs (miRNAs) derived from viruses, have been detected in body fluids and are known to regulate the expression of host genes. Recent evidence indicates that SARS-CoV-2-encoded miRNAs could contribute to pulmonary disease. Pulmonary fibrosis is an important complication in SARS-CoV-2 infected patients, either during hospitalization or after discharge, however, the underlying mechanisms are not fully elucidated. Here, we report a SARS-CoV-2-encoded miRNA, miR-nsp3-3p, facilitates host pulmonary fibrosis by inhibiting expression of activated leukocyte cell adhesion molecule (ALCAM) and promoting epithelial-mesenchymal transition (EMT). First, we detected miR-nsp3-3p in clinical specimens and found it was remarkably increased in throat swabs and alveolar lavage fluids from severe/critical COVID-19 patients compared to control groups or mild/moderate patients. We further revealed that adeno-associated virus (AAV)-nsp3 infection can induce pulmonary fibrosis in BALB/c mice while miR-nsp3-3p antagomirs can reverse that, and ALCAM was found to be as a target gene of miR-nsp3-3p. miR-nsp3-3p overexpression can inhibit the expression of ALCAM and promote EMT of pulmonary epithelial cells. Moreover, overexpression of ALCAM can reverse the miR-nsp3-3p-induced EMT and fibrosis. These findings highlight the essential role of SARS-CoV-2-encoded miRNAs in promoting the pathological progression of lung disease, and provide novel insights into the interactions between viral miRNAs and host pathology.
基金supported by a Jérome Lejeune Foundation award and a Kent State University Innovation Research Seed Award to KW
文摘During development and regeneration,axonal growth depends on a rapid response to extracellular growth and guidance molecules.One mechanism underlying this rapid response is local protein synthesis（Jung et al.,2012）.Local protein synthesis is a highly tuned,
基金supported by grants from the Spanish Ministerio de Economía y Competitividad(Plan Nacional I+D+i,SAF2013-46151-R and SAF2016-80535-R to FL),co-financed by the European Development Regional Fund‘A way to achieve Europe’ERDFsupported by the Sara Borrell fellowship CD15/00016 from Instituto de Salud Carlos Ⅲ.
文摘Psoriasis is a chronic inflammatory skin disease with a strong genetic background and is triggered by environmental factors.Available evidence supports CD6,a lymphocyte surface receptor mostly expressed by T cells,as a putative target in autoimmunity.Accordingly,a humanized anti-CD6 antibody has been assayed for the treatment of certain autoimmune disorders,including psoriasis.Here,we present novel evidence in mice and humans for a direct involvement of CD6 in psoriasis pathophysiology.First,an attenuated form of imiquimod-induced psoriasis-like skin inflammation was demonstrated in CD6-deficient mice,as deduced from lower epidermal thickness and local reduced production of pro-inflammatory cytokines,namely,interleukin-17A.Thus,isolated CD4+CD62L+T cells from CD6-deficient mice displayed decreased in vitro T-helper type 17 polarization.Second,a statistically significant association between CD6 single-nucleotide polymorphisms(rs17824933,rs11230563 and rs12360861)and more severe forms of psoriasis was demonstrated in a cohort of 304 patients at three public hospitals from the metropolitan area of Barcelona.Taken together,these results provide new supportive evidence of the contribution of the CD6 lymphocyte receptor in psoriasis at both experimental and clinical levels.
