MiR-430 is a non-coding small RNA that participates in early embryonic development by acting on the Nodal signaling pathway.Its functions in Paralichthys olivaceus(P.olivaceus),however,remain unclear.In this study,thr...MiR-430 is a non-coding small RNA that participates in early embryonic development by acting on the Nodal signaling pathway.Its functions in Paralichthys olivaceus(P.olivaceus),however,remain unclear.In this study,through biological information technology,we hypothesized lefty was the target gene of miR-430.Lefty is a divergent member of the transforming growth factor-β(TGF-β)superfamily,and is involved in regulating left-right patterning as an antagonist of the Nodal signaling pathway.To study the relationship between miR-430 and lefty gene,miR-430 and fluorescent expression vector were transfected into embryo cells.Our results showed that miR-430 has important effects on early embryonic development.It can inhibit the expressions of lefty and other genes related to Nodal signaling pathway.Additionally,the expression of miR-430 was involved in the metamorphosis of P.olivaceus.This study clarifies the function of miR-430 in P.olivaceus,which will be helpful for further research on the interactions between miR-430 and the Nodal signaling pathway.展开更多
Liver fibrosis is the deposition of extracellular matrix(ECM)in the liver caused by persistent chronic injury,which can lead to more serious diseases such as cirrhosis or cancer.Blocking the effect of transforming gro...Liver fibrosis is the deposition of extracellular matrix(ECM)in the liver caused by persistent chronic injury,which can lead to more serious diseases such as cirrhosis or cancer.Blocking the effect of transforming growth factorβ1(TGF-β1),one of the most important cytokines in liver fibrosis,may be one of the effective ways to inhibit liver fibrosis.As a kind of natural nano-scale vesicles,small extracellular vesicles(sEvs)have displayed excellent delivery vehicle properties.Herein,we prepared hepatic stellate cell(HSC)-derived sEvs loading left-right determination factor 1(lefty1)mRNA(sEvLs)and we wanted to verify whether they can inhibit fibrosis by blocking the TGF-β1 signaling pathway.The results showed that sEvLs had effective cell uptake and reduced activation of HSCs.Rats that were injected with CCl 4 by intraperitoneal injection for 6 weeks exhibited obvious symptoms of liver fibrosis and were treated with systemically administered sEvLs and free sEvs for 4 weeks.Rats injected with olive oil alone served as sham controls.Administration of sEvLs significantly reduced the area of fibrosis compared with free sEvs.We demonstrated that sEvLs inhibited HSCs activation and ECM production,and promote ECM degradation by downregulatingα-smooth muscle actin(α-SMA),collagen I,tissue inhibitor of metalloproteinase(TIMP)-1 and upregulating matrix metalloprotease(MMP)-1.In summary,as an endogenous delivery vehicle,sEvs could deliver mRNA to attenuate hepatic fibrosis by blocking the TGF-β/Smad signaling pathway.展开更多
基金supported by the National Natural Sci-ence Foundation of China(No.31372511)the Fun-damental Research Funds for the Central Universities(No.201822026)
文摘MiR-430 is a non-coding small RNA that participates in early embryonic development by acting on the Nodal signaling pathway.Its functions in Paralichthys olivaceus(P.olivaceus),however,remain unclear.In this study,through biological information technology,we hypothesized lefty was the target gene of miR-430.Lefty is a divergent member of the transforming growth factor-β(TGF-β)superfamily,and is involved in regulating left-right patterning as an antagonist of the Nodal signaling pathway.To study the relationship between miR-430 and lefty gene,miR-430 and fluorescent expression vector were transfected into embryo cells.Our results showed that miR-430 has important effects on early embryonic development.It can inhibit the expressions of lefty and other genes related to Nodal signaling pathway.Additionally,the expression of miR-430 was involved in the metamorphosis of P.olivaceus.This study clarifies the function of miR-430 in P.olivaceus,which will be helpful for further research on the interactions between miR-430 and the Nodal signaling pathway.
基金received from National Natural Science Foundation of China(No.82073784)Jilin Province Science and Technology Development Program(No.20200801012GH)Industrial Technology Research and Development Projects from the Development and Reform Commission of Jilin Province(2019C050-4).
文摘Liver fibrosis is the deposition of extracellular matrix(ECM)in the liver caused by persistent chronic injury,which can lead to more serious diseases such as cirrhosis or cancer.Blocking the effect of transforming growth factorβ1(TGF-β1),one of the most important cytokines in liver fibrosis,may be one of the effective ways to inhibit liver fibrosis.As a kind of natural nano-scale vesicles,small extracellular vesicles(sEvs)have displayed excellent delivery vehicle properties.Herein,we prepared hepatic stellate cell(HSC)-derived sEvs loading left-right determination factor 1(lefty1)mRNA(sEvLs)and we wanted to verify whether they can inhibit fibrosis by blocking the TGF-β1 signaling pathway.The results showed that sEvLs had effective cell uptake and reduced activation of HSCs.Rats that were injected with CCl 4 by intraperitoneal injection for 6 weeks exhibited obvious symptoms of liver fibrosis and were treated with systemically administered sEvLs and free sEvs for 4 weeks.Rats injected with olive oil alone served as sham controls.Administration of sEvLs significantly reduced the area of fibrosis compared with free sEvs.We demonstrated that sEvLs inhibited HSCs activation and ECM production,and promote ECM degradation by downregulatingα-smooth muscle actin(α-SMA),collagen I,tissue inhibitor of metalloproteinase(TIMP)-1 and upregulating matrix metalloprotease(MMP)-1.In summary,as an endogenous delivery vehicle,sEvs could deliver mRNA to attenuate hepatic fibrosis by blocking the TGF-β/Smad signaling pathway.
