title: Down-regulation of focal adhesion kinase by short hairpin RNA increased apoptosis of rat hepatic stellate cells.
abstract: Focal adhesion kinase (FAK) plays an essential role in the activation of hepatic stellate cells (HSC). The role of FAK on proliferation and apoptosis of fibronectin (FN)-stimulated HSC was investigated using short hairpin RNA (shRNA)-mediated gene silencing technology. FAK shRNA decreased the expressions of FAK, p-FAK (Tyr(397)), ERK(1), and p-ERK(1). FAK gene silencing also inhibited HSC proliferation by 11.08% at 12-h, 15.12% at 24-h, and 28.62% at 48-h post-transfection. Flow cytometric analysis (FACS) revealed that the apoptotic rate at 24 h was increased in the FAK shRNA plasmid group compared with the HK group (8.29 ± 0.79% vs 2.70 ± 0.31%, p < 0.01). TUNEL also confirmed the increase in the rate of apoptosis (19.00 ± 0.92% vs 7.63 ± 0.70%, p < 0.01), and studies showed that the caspase-3 expression was increased while the ratio of Bcl-2 to Bax was decreased. Together, these data show that FAK regulates HSC proliferation and induces the apoptosis of HSC via the caspase-3 and Bcl-2/Bax pathway.
authors.affiliation: Department of Gastroenterology, The Second Hospital of Hebei Medical University, Shijiazhuang, China.
authors.forename: Junyan
authors.initials: J
authors.lastname: An
authors.forename: Libo
authors.initials: L
authors.lastname: Zheng
authors.forename: Shurui
authors.initials: S
authors.lastname: Xie
authors.forename: Zhina
authors.initials: Z
authors.lastname: Dun
authors.forename: Lisen
authors.initials: L
authors.lastname: Hao
authors.forename: Dongmei
authors.initials: D
authors.lastname: Yao
authors.forename: David Q
authors.initials: DQ
authors.lastname: Shih
authors.forename: Xiaolan
authors.initials: X
authors.lastname: Zhang
mesh_terms: D000818:Animals; D017209:Apoptosis; D053148:Caspase 3 / Q000235:genetics / Q000378:metabolism; D002460:Cell Line; D049109:Cell Proliferation; D015536:Down-Regulation; D005353:Fibronectins / Q000378:metabolism; D051417:Focal Adhesion Kinase 1 / Q000235:genetics / Q000378:metabolism*; D020868:Gene Silencing; D055166:Hepatic Stellate Cells / Q000166:cytology* / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000235:genetics / Q000378:metabolism; D010957:Plasmids / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics*; D051381:Rats; D014162:Transfection; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: C494828:Bax protein, rat; D005353:Fibronectins; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D051028:bcl-2-Associated X Protein; D051417:Focal Adhesion Kinase 1; C496052:Ptk2 protein, rat; D048052:Mitogen-Activated Protein Kinase 3; C505410:Casp3 protein, rat; D053148:Caspase 3