| Hou CC |
------>authors3_c=None ------>paper_class1=1 ------>Impact_Factor=None ------>paper_class3=2 ------>paper_class2=1 ------>vol=166 ------>confirm_bywho=shiemin ------>insert_bywho=tsohsiao ------>Jurnal_Rank=None ------>authors4_c=None ------>comm_author= ------>patent_EDate=None ------>authors5_c=None ------>publish_day=None ------>paper_class2Letter=None ------>page2=771 ------>medlineContent= ------>unit=E0100 ------>insert_date=20050731 ------>iam=5 ------>update_date=None ------>author=??? ------>change_event=4 ------>ISSN=None ------>authors_c=None ------>score=500 ------>journal_name=Am J Pathol ------>paper_name=Ultrasound-microbubble-mediated gene transfer of inducible Smad7 blocks transforming growth factor-beta signaling and fibrosis in rat remnant kidney ------>confirm_date=20050817 ------>tch_id=090107 ------>pmid=15743788 ------>page1=761 ------>fullAbstract=Transforming growth factor (TGF)-beta1 has been shown to play a critical role in hypertensive nephropathy. We hypothesized that blocking TGF-beta1 signaling could attenuate renal fibrosis in a rat model of remnant kidney disease. Groups of six rats were subjected to 5/6 nephrectomy and received renal arterial injection of a doxycycline-regulated Smad7 gene or control empty vector using an ultrasound-microbubble-mediated system. Smad7 transgene expression within the kidney was tightly controlled by the addition of doxycycline in the daily drinking water. All animals were euthanized at week 4 for renal functional and histological examination. Hypertension of equivalent magnitude (190 to 200 mmHg) developed in both Smad7- and empty vector-treated rats. However, treatment with Smad7 substantially inhibited Smad2/3 activation and prevented progressive renal injury by inhibiting the rise of 24-hour proteinuria (P < 0.001) and serum creatinine (P < 0.001), preserving creatinine clearance (P < 0.05), and attenuating renal fibrosis and vascular sclerosis such as collagen I and III expression (P < 0.01) and myofibroblast accumulation (P < 0.001). In conclusion, TGF-beta/Smad signaling plays a critical role in renal fibrosis in a rat remnant kidney model. The ability of Smad7 to block Smad2/3 activation and attenuate renal and vascular sclerosis demonstrates that ultrasound-mediated Smad7 gene therapy may be a useful therapeutic strategy for the prevention of renal fibrosis in association with hypertension. ------>tmu_sno=None ------>sno=11627 ------>authors2=Wang W ------>authors3=Huang XR ------>authors4=Fu P ------>authors5=Chen TH ------>authors6=Sheikh-Hamad D, Lan HY ------>authors6_c=None ------>authors=Hou CC ------>delete_flag=0 ------>SCI_JNo=None ------>authors2_c=None ------>publish_area=None ------>updateTitle=Ultrasound-microbubble-mediated gene transfer of inducible Smad7 blocks transforming growth factor-beta signaling and fibrosis in rat remnant kidney. ------>language=2 ------>check_flag=None ------>submit_date=None ------>country=None ------>no=3 ------>patent_SDate=None ------>update_bywho=None ------>publish_year=2005 ------>submit_flag=None ------>publish_month=None |