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| 1 | Adipose-derived stem cells inhibit dermal fibroblast growth and induce apoptosis in keloids through the arachidonic acid-derived cyclooxygenase-2/prostaglandin E2 cascade by paracrine显示文摘Background:The clinical features of keloids consist of aberrant proliferation,secretion,differentiation and apoptosis of keloid dermis-derived fibroblasts(KFBs).Notably,the apoptosis rate of KFBs is lower than the proliferation rate.Though the anti-fibrotic effect of adipose-derived stem cells(ADSCs)on keloids has become a hot topic of research,the exact anti-fibrotic mechanism of the paracrine effect remains unclear.This study aimed to find out how the conditioned medium of ADSCs(ADSC-CM)exerts an anti-fibrotic effect in KFBs.Methods:KFBs and ADSCs were extracted and cultured.Then,ADSC-CM was prepared.Whether ADSC-CM could inhibit KFB growth and induce apoptosis was verified by the use of a cell counting kit-8,an 5-Ethynyl-2-deoxyuridine(Edu)kit and flow cytometry.The expressions of cyclooxygenase-1(COX-1),COX-2,caspase 3 and B-cell lymphoma-2(Bcl-2)in ADSC-CM-cultured KFBs were tested by real-time PCR and western blotting.To clarify the role of COX-2 in ADSC-CM-induced KFB apoptosis,a specific COX-2 inhibitor,celecoxib,was applied to KFBs cultured in ADSC-CM.Moreover,we tested the production of arachidonic acid(AA)and prostaglandin E2(PGE2)by ELISA.Then,we established a keloid transplantation model in a nude mouse to validate the therapeutic effect in vivo.Results:The proliferation ability of KFBs cultured in ADSC-CM was found to be weakened and apoptosis was significantly increased.Caspase 3 expression was significantly upregulated and Bcl-2 was downregulated in ADSC-CM-cultured KFBs.Furthermore,ADSC-CM strikingly elevated COX-2 mRNA and protein expressions,but COX-1 expression was unaltered.COX-2 inhibitors reduced ADSC-CM-induced apoptosis.Additionally,COX-2 inhibition blocked the elevation of caspase 3 and reversed the decrease in Bcl-2 expression.ADSC-CM increased PGE2 levels by 1.5-fold and this effect was restrained by COX-2 inhibition.In the nude mouse model,expressions of AA,COX-2 and PGE2 were higher in the translated keloid tissues after ADSC-CM injection than in the controls.Conclusions:We showed activation of the COX-2/PGE2 cascade in KFBs in response to ADSC-CM.By employing a specific COX-2 inhibitor,COX-2/PGE2 cascade activation played a crucial role in mediating the ADSC-CM-induced KFB apoptosis and anti-proliferation effects. | Jinxiu Yang Shiyi Li Leren He Minliang Chen | 2021 | Burns & Trauma2021，9，1： | 4 |
| 2 | Mutations in the PCSK9 gene in Norwegian sub- jects with autosomal dominant hypercholesterolemia显示文摘 | Leren TP | 2004 | Clin Genet2004，65，5： | 1 |
| 3 | Missense mutations in the PCSK9 gene are associated with hypocholesterolemia and possibly increased response to statin therapy显示文摘 | Berge K E Ose L Leren T P | 2006 | Arterioscler Thromb Vase Biol2006，26，5： | 1 |
| 4 | Jervell and Lange-Nielsen syndrome in Norwegian children: aspects around cochlear implantation, hearing, and balance显示文摘 | Siem G Friih A Leren TP | 2008 | Ear Hear2008，29，2： | 1 |
| 5 | Fragmentatior: at:tdy of five trichothecenes using electrospray hybrid ion trap/time-of-flight maaa spectrometry with accurate mass measurements 显示文摘 | Liu Zhao Ying Yu Chun Hong Wan Leren | 2012 | International Journal of Mass Spectrometry2012，309，1： | 1 |
| 6 | Pregnacy outcomes in familial hypercholesterolemia: a registry - based study 显示文摘 | Toleikyte I Retterstl K Leren TP | 2011 | Circulation2011，124，15： | 1 |
| 7 | Incorporating demand response with spinning reserve to realize an adaptive frequency restoration plan for system contingencies显示文摘 | Chang-Chien Leren An L N Lin T W | 2012 | IEEE Transactions on Smart Grid2012，3，3： | 1 |
| 8 | The unique role of proprotein convertase subtilisin/kexin 9 in cholesterol homeostasis显示文摘 | Mousavi SA Berge KE Leren TP | 2009 | J Intern Med2009，266，6： | 1 |
| 9 | High prevalence of ex-ercise -induced arrhythmias in catecholaminergic polymorpicventricular tachycardia mutation - positive family members diag-nosed by cascade genetic screening 显示文摘 | Haugaa K H Leren I S BergeK E | 2010 | Europace2010，12，3： | 1 |
| 10 | A vohage-doubling method for measuring the voltage dependence of compressed gas capacitors 显示文摘 | Latzel H G Wang Leren | 1987 | IEEE Trans IM1987，36，3： | 1 |
| 11 | Mutations in the PCSK9 gene in Norwegian subjects with autosomal dominant hypercholesterolemia显示文摘 | LEREN T P | 2004 | Clin Genet2004，65，： | 1 |
| 12 | Coronary heart disease and treatment of hypertension Some Oslo Study data显示文摘 | Leren P Helgeland A | 1986 | Am J Med1986，80，2： | 1 |
| 13 | Effects of posture on serum cholesterol {ractions,cholesterol ratio and triglycerides显示文摘 | Kjeldsen SE Eide I Leren P | 1983 | Scand J Clin Lab Invest1983，43，2： | 1 |
| 14 | Mutations in the PCSK9 gene in Norwegian subjects with autosomal dominant hypercholesterolemia 显示文摘 | Leren TP | 2004 | Cliff Genet2004，65，5： | 1 |
| 15 | Multiple dysfunctions of two apolip oprotein A-I (R160L) also and apoA-I (P165R), that are associated with hypoalphali poproteinemia in heterozy- gous carriers显示文摘 | Daum U Leren TP Langer C | 1999 | J Lipid Res1999，40，3： | 1 |
| 16 | Mutations in the pcsk9 gene in Norwegian subjects with automal dominant hypercholesterolemia显示文摘 | Leren TP | 2004 | Clin Genet2004，65，5： | 1 |
| 17 | Molecular genetics of familial hypercholexterolaemia in Norway显示文摘 | Leren TP | 1997 | J Intern Med1997，241，： | 1 |
| 18 | Missense Mutations in the PCSK9 gene are associated with hypocholesterolemia and possibly increased response to statin therapy 显示文摘 | Berge KE Ose L Leren TP | 2006 | Arterioscler Thromb Vasc Biol2006，10，： | 1 |
| 19 | Parasitic leiomyo-mas after laparoscopic surgery with morcellation 显示文摘 | Leren V Langebrekke A Qvigstad E | 2012 | ActaObstet Gynecol Scand2012，91，10： | 1 |
| 20 | New SCN5A mutation in a SUDEP victim with idiopathic epilepsy显示文摘 | Aurlien D Leren TP | | 0，，02： | 1 |
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