title: Efficient delivery of connective tissue growth factor shRNA using PAMAM nanoparticles.
abstract: The aim of this study was to detect the anti-fibrosis activity of connective tissue growth factor (CTGF) small hairpin RNA (shRNA) mediated by polyamidoamine dendrimer nanoparticles in rat myocardial cell lines and myocardium. CTGF shRNAs were constructed from inverted oligonucleotides and a polyamidoamine nanoparticle vector was used to transfer shRNA into H9c2 myocardial cells and spontaneously hypertensive rats. The expression of CTGF, transforming growth factor-b1, and laminin were measured by semi-quantitative reverse transcription-polymerase chain reaction, Western blotting, and immunohistochemistry. pCTGF-shRNA significantly reduced CTGF upregulation induced by angiotensin II in H9c2 myocardial cells. The mRNA and protein expression of CTGF and laminin in pCTGF-shRNA-transferred spontaneously hypertensive rats decreased significantly compared to the control group and pHK-shRNA group (P < 0.05). The expression of transforming growth factor-b1 showed no significant difference among the 3 groups (P > 0.05). pCTGF-shRNA mediated by polyamidoamine can be used to successfully reduce myocardial CTGF and laminin expression, suggesting that this system can be used to improve myocardial fibrosis therapy.
authors.affiliation: Center of Clinical Pharmacology, The Third Xiangya Hospital, Central South University, Changsha, China.
authors.forename: Z J
authors.initials: ZJ
authors.lastname: Huang
authors.affiliation: Department of Nephrology, The Third Xiangya Hospital, Central South University, Changsha, China BinYIdoc@163.com.
authors.forename: B
authors.initials: B
authors.lastname: Yi
authors.affiliation: Center of Clinical Pharmacology, The Third Xiangya Hospital, Central South University, Changsha, China.
authors.forename: H
authors.initials: H
authors.lastname: Yuan
authors.affiliation: Center of Clinical Pharmacology, The Third Xiangya Hospital, Central South University, Changsha, China.
authors.forename: G P
authors.initials: GP
authors.lastname: Yang
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002460:Cell Line; D055513:Connective Tissue Growth Factor / Q000235:genetics* / Q000378:metabolism; D050091:Dendrimers / Q000737:chemistry; D015870:Gene Expression; D007150:Immunohistochemistry; D007797:Laminin / Q000235:genetics / Q000378:metabolism; D008297:Male; D009206:Myocardium / Q000166:cytology / Q000378:metabolism; D053758:Nanoparticles / Q000008:administration & dosage* / Q000737:chemistry; D011073:Polyamines / Q000737:chemistry; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000008:administration & dosage* / Q000737:chemistry / Q000235:genetics; D011918:Rats, Inbred SHR; D020133:Reverse Transcriptase Polymerase Chain Reaction; D053773:Transforming Growth Factor beta1 / Q000235:genetics / Q000378:metabolism
chemical_list: C526316:CCN2 protein, rat; D050091:Dendrimers; D007797:Laminin; C531249:Poly(amidoamine); D011073:Polyamines; D034741:RNA, Small Interfering; D053773:Transforming Growth Factor beta1; D055513:Connective Tissue Growth Factor