title: Rapamycin-Induced apoptosis in HGF-stimulated lens epithelial cells by AKT/mTOR, ERK and JAK2/STAT3 pathways.
abstract: Hepatocyte growth factor (HGF) induced the proliferation of lens epithelial cells (LECs) and may be a major cause of posterior capsule opacification (PCO), which is the most frequent postoperative complication of cataract surgery. To date, several agents that can block LECs proliferation have been studied, but none have been used in clinic. Recently, accumulating evidence has suggested rapamycin, the inhibitor of mTOR (mammalian target of Rapamycin), was associated with the induction of apoptosis in LECs. The purpose of our study was to investigate the potential effects of rapamycin on HGF-induced LECs and the underlying mechanisms by which rapamycin exerted its actions. Using cell proliferation, cell viability and flow cytometric apoptosis assays, we found that rapamycin potently not only suppressed proliferation but also induced the apoptosis of LECs in a dose-dependent manner under HGF administration. Further investigation of the underlying mechanism using siRNA transfection revealed that rapamycin could promote apoptosis of LECs via inhibiting HGF-induced phosphorylation of AKT/mTOR, ERK and JAK2/STAT3 signaling molecules. Moreover, the forced expression of AKT, ERK and STAT3 could induce a significant suppression of apoptosis in these cells after treatment of rapamycin. Together, these findings suggested that rapamycin-induced apoptosis in HGF-stimulated LECs is accompanied by inhibition of AKT/mTOR, ERK and JAK2/STAT3 pathways, which supports its use to inhibit PCO in preclinical studies and provides theoretical foundation for future possible practice.
authors.affiliation: Tianjin Medical University Eye Hospital& Eye Institute, No. 251, Fu Kang Road, Nan Kai District, Tianjin 300384, China. tianfang1216@126.com.
authors.forename: Fang
authors.initials: F
authors.lastname: Tian
authors.affiliation: Tianjin Medical University Eye Hospital& Eye Institute, No. 251, Fu Kang Road, Nan Kai District, Tianjin 300384, China. aitaomubang@126.com.
authors.forename: Lijie
authors.initials: L
authors.lastname: Dong
authors.affiliation: Tianjin Medical University Eye Hospital& Eye Institute, No. 251, Fu Kang Road, Nan Kai District, Tianjin 300384, China. snail.mutou@163.com.
authors.forename: Yu
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: Tianjin Medical University Eye Hospital& Eye Institute, No. 251, Fu Kang Road, Nan Kai District, Tianjin 300384, China. 13752613234@163.com.
authors.forename: Yan
authors.initials: Y
authors.lastname: Shao
authors.affiliation: Tianjin Medical University Eye Hospital& Eye Institute, No. 251, Fu Kang Road, Nan Kai District, Tianjin 300384, China. wenboli0412@126.com.
authors.forename: Wenbo
authors.initials: W
authors.lastname: Li
authors.affiliation: Tianjin Medical University Eye Hospital& Eye Institute, No. 251, Fu Kang Road, Nan Kai District, Tianjin 300384, China. tmuechong@sina.com.
authors.forename: Hong
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Tianjin Medical University Eye Hospital& Eye Institute, No. 251, Fu Kang Road, Nan Kai District, Tianjin 300384, China. wangfei@berkgen.com.
authors.forename: Fei
authors.initials: F
authors.lastname: Wang
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D004847:Epithelial Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D017228:Hepatocyte Growth Factor / Q000494:pharmacology*; D006801:Humans; D053614:Janus Kinase 2 / Q000378:metabolism; D007908:Lens, Crystalline / Q000166:cytology*; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D050796:STAT3 Transcription Factor / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*; D020123:Sirolimus / Q000494:pharmacology*; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism
chemical_list: D050796:STAT3 Transcription Factor; D017228:Hepatocyte Growth Factor; C546842:MTOR protein, human; C507924:JAK2 protein, human; D053614:Janus Kinase 2; D051057:Proto-Oncogene Proteins c-akt; D058570:TOR Serine-Threonine Kinases; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D020123:Sirolimus