Mitofusion 2 Overexpression Decreased Proliferation of Human Embryonic Lung Fibroblasts in Acute Respiratory Distress Syndrome through Inhibiting RAS-RAF-1-ERK1/2 Pathway

Acute respiratory distress syndrome(ARDS)is one of the most fatal diseases worldwide.Pulmonary fibrosis occurs early in ARDS,and its severity plays a crucial role in ARDS mortality rate.Some studies suggested that fibroproliferation is an essential mechanism in ARDS.Mitofusion2(Mfn2)overexpression plays a role in inhibiting cell proliferation.However,the role and potential mechanism of Mfn2 on the proliferation of fibroblasts is still unknown.In this study,we aimed at exploring the effect of Mfn2 on the human embryonic lung fibroblasts(HELF)and discussed its related mechanism.The HELF were treated with the Mfn2 overexpressing lentivirus(adv-Mfn2).The cell cycle was detected by flow cytometry.MTT,PCR and Western blotting were used to investigate the effect of Mfn2 on the proliferation of the HELF,collagen expression,the RAS-RAF-1-ERK1/2 pathway and the expression of cycle-related proteins(p21,p27,Rb,Raf-1,p-Raf-1,Erk1/2 and p-Erk1/2).The co-immunoprecipitation assay was used to explore the interaction between Mfn2 and Ras.The results showed that the overexpression of Mfn2 inhibited the proliferation of the HELF and induced the cell cycle arrest at the G0/G1 phase.Meanwhile,Mfn2 also inhibited the expression of collagen I,p-Erk and p-Raf-1.In addition,an interaction between Mfn2 and Ras existed in the HELF.This study suggests that the overexpression of Mfn2 can decrease the proliferation of HELF in ARDS,which was associated with the inhibition of the RAS-RAF-1-ERK1/2 pathway.The results may offer a potential therapeutic intervention for patients with ARDS.

Novel antioxidant peptide from broken rice resist H_(2)O_(2)-induced premature senescence in 2BS cells via PI3K/Akt and JNK/Bax signaling pathway

SGDWSDIGGR(S-10-R)is a kind of antioxidant peptide derived from broken rice.In the present study,the effects of S-10-R against H_(2)O_(2)-induced cell damage and premature senescence in 2BS cells were determined.The results indicated that S-10-R could improve cell viability and mitochondrial membrane potential at least 1.06 and 1.12 folds compared with senescence cells.Moreover,S-10-R inhibitedβ-galactosidase,and DNA damage alleviates the effect on 2BS senescence cells due to scavenging ROS.The apoptosis rate can be reduced by 80.58%.Furthermore,S-10-R could inhibit PI3K and Akt phosphorylation,downregulate Bax and caspases-3 expression,and inhibit premature senescence through activating PI3K/Akt related intrinsic apoptotic signaling pathways and suppressing JNK/Bcl-2 related mitochondria-dependent apoptosis.The present study confirmed the feasibility of antioxidants as anti-aging drugs,as well as provided a substantial basis for future application of S-10-R as a functional ingredient against oxidative stress-induced premature aging.