{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,10]],"date-time":"2026-02-10T07:19:40Z","timestamp":1770707980721,"version":"3.49.0"},"reference-count":43,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2020,2,1]],"date-time":"2020-02-01T00:00:00Z","timestamp":1580515200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["17K19496"],"award-info":[{"award-number":["17K19496"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["18J10186"],"award-info":[{"award-number":["18J10186"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Nagai Memorial Research Scholarship from the Pharmaceutical Society of Japan","award":["N-177001"],"award-info":[{"award-number":["N-177001"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceutics"],"abstract":"<jats:p>We previously developed a renal pressure-mediated transfection method (renal pressure method) as a kidney-specific in vivo gene delivery system. However, additional information on selecting other injection routes and applicable animals remains unclear. In this study, we selected renal arterial and ureteral injections as local administration routes and evaluated the characteristics of gene delivery such as efficacy, safety, and distribution in pressured kidney of rat. Immediately after the naked pDNA injection, via renal artery or ureter, the left kidney of the rat was pressured using a pressure controlling device. Transfection efficiency of the pressured kidney was about 100-fold higher than that of the injection only group in both administration routes. The optimal pressure intensity in the rat kidney was 1.2 N\/cm2 for renal arterial injection and 0.9 N\/cm2 for ureteral injection. We found that transgene expression site differs according to administration route: cortical fibroblasts and renal tubule in renal arterial injection and cortical and medullary tubule and medullary collecting duct in ureteral injection. This is the first report to demonstrate that the renal pressure method can also be effective, after renal arterial and ureteral injections, in rat kidney.<\/jats:p>","DOI":"10.3390\/pharmaceutics12020114","type":"journal-article","created":{"date-parts":[[2020,2,3]],"date-time":"2020-02-03T01:25:51Z","timestamp":1580693151000},"page":"114","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Effects of Tissue Pressure on Transgene Expression Characteristics via Renal Local Administration Routes from Ureter or Renal Artery in the Rat Kidney"],"prefix":"10.3390","volume":"12","author":[{"given":"Natsuko","family":"Oyama","sequence":"first","affiliation":[{"name":"Graduate School of Biomedical Sciences, Nagasaki University, 1-7-1 Sakamoto, Nagasaki-shi, Nagasaki 852-8588, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Haruyuki","family":"Takahashi","sequence":"additional","affiliation":[{"name":"Graduate School of Pharmaceutical Sciences, Kyoto University, 46-29 Yoshida-Shimo-Adachi-cho, Sakyo-ku, Kyoto 606-8501, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maho","family":"Kawaguchi","sequence":"additional","affiliation":[{"name":"Graduate School of Biomedical Sciences, Nagasaki University, 1-7-1 Sakamoto, Nagasaki-shi, Nagasaki 852-8588, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hirotaka","family":"Miyamoto","sequence":"additional","affiliation":[{"name":"Graduate School of Biomedical Sciences, Nagasaki University, 1-7-1 Sakamoto, Nagasaki-shi, Nagasaki 852-8588, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Koyo","family":"Nishida","sequence":"additional","affiliation":[{"name":"Graduate School of Biomedical Sciences, Nagasaki University, 1-7-1 Sakamoto, Nagasaki-shi, Nagasaki 852-8588, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Masako","family":"Tsurumaru","sequence":"additional","affiliation":[{"name":"Graduate School of Biomedical Sciences, Nagasaki University, 1-7-1 Sakamoto, Nagasaki-shi, Nagasaki 852-8588, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mikiro","family":"Nakashima","sequence":"additional","affiliation":[{"name":"Graduate School of Biomedical Sciences, Nagasaki University, 1-7-1 Sakamoto, Nagasaki-shi, Nagasaki 852-8588, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fumiyoshi","family":"Yamashita","sequence":"additional","affiliation":[{"name":"Graduate School of Pharmaceutical Sciences, Kyoto University, 46-29 Yoshida-Shimo-Adachi-cho, Sakyo-ku, Kyoto 606-8501, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mitsuru","family":"Hashida","sequence":"additional","affiliation":[{"name":"Graduate School of Pharmaceutical Sciences, Kyoto University, 46-29 Yoshida-Shimo-Adachi-cho, Sakyo-ku, Kyoto 606-8501, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shigeru","family":"Kawakami","sequence":"additional","affiliation":[{"name":"Graduate School of Biomedical Sciences, Nagasaki University, 1-7-1 Sakamoto, Nagasaki-shi, Nagasaki 852-8588, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2020,2,1]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"426","DOI":"10.1038\/sj.gt.3300406","article-title":"Kidney-targeted liposome-mediated gene transfer in mice","volume":"4","author":"Lai","year":"1997","journal-title":"Gene Ther."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"455","DOI":"10.1089\/10430340252792585","article-title":"Kidney-targeted naked DNA transfer by retrograde renal vein injection in rats","volume":"13","author":"Maruyama","year":"2002","journal-title":"Hum. Gene Ther."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"618","DOI":"10.1038\/gt.2014.35","article-title":"rAAV9 combined with renal vein injection is optimal for kidney-targeted gene delivery: Conclusion of a comparative study","volume":"21","author":"Rocca","year":"2014","journal-title":"Gene Ther."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"949","DOI":"10.1681\/ASN.V125949","article-title":"Electroporation-mediated gene transfer that targets glomeruli","volume":"12","author":"Tsujie","year":"2001","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"343","DOI":"10.1002\/jgm.2931","article-title":"Glomeruli or interstitium targeted by inter-renal injections supplemented by electroporation: Still a useful tool in renal research","volume":"18","author":"Mao","year":"2016","journal-title":"J Gene Med."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"383","DOI":"10.1016\/j.bbrc.2008.04.097","article-title":"Renal press-mediated transfection method for plasmid DNA and siRNA to the kidney","volume":"372","author":"Mukai","year":"2008","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1157","DOI":"10.1089\/hum.2008.213","article-title":"Pressure-mediated transfection of murine spleen and liver","volume":"20","author":"Mukai","year":"2009","journal-title":"Hum. Gene Ther."},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Shimizu, K., Kawakami, S., Hayashi, K., Kinoshita, H., Kuwahara, K., Nakao, K., Hashida, M., and Konishi, S. (2012). In vivo site-specific transfection of naked plasmid DNA and siRNAs in mice by using a tissue suction device. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0041319"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"450","DOI":"10.3109\/1061186X.2015.1087526","article-title":"Optimization of renal transfection using a renal suction-mediated transfection method in mice","volume":"24","author":"Taniguchi","year":"2016","journal-title":"J. Drug Target"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"906","DOI":"10.1080\/10717544.2017.1333171","article-title":"Characterization of transgene expression and pDNA distribution of the suctioned kidney in mice","volume":"24","author":"Oyama","year":"2017","journal-title":"Drug Deliv."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"2309","DOI":"10.2147\/IJN.S157375","article-title":"Efficient gene transfection to the brain with ultrasound irradiation in mice using stabilized bubble lipopolyplexes prepared by the surface charge regulation method","volume":"13","author":"Ogawa","year":"2018","journal-title":"Int. J. Nanomed."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"4481","DOI":"10.1021\/acs.molpharmaceut.8b00476","article-title":"Development of High-Functionality and -Quality Lipids with RGD Peptide Ligands: Application for PEGylated Liposomes and Analysis of Intratumoral Distribution in a Murine Colon Cancer Model","volume":"15","author":"Suga","year":"2018","journal-title":"Mol. Pharm."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Nishimura, K., Yonezawa, K., Fumoto, S., Miura, Y., Hagimori, M., Nishida, K., and Kawakami, S. (2019). Application of Direct Sonoporation from a Defined Surface Area of the Peritoneum: Evaluation of Transfection Characteristics in Mice. Pharmaceutics, 11.","DOI":"10.3390\/pharmaceutics11050244"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1551","DOI":"10.1111\/j.1523-1755.2004.05409.x","article-title":"Gene therapy in renal diseases","volume":"65","author":"Imai","year":"2004","journal-title":"Kidney Int."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1016\/j.bbrc.2018.01.169","article-title":"Nephron segment-specific gene expression using AAV vectors","volume":"497","author":"Asico","year":"2018","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1111\/j.1440-1797.2007.00907.x","article-title":"Renal artery injection for delivery of biological materials to the glomerulus","volume":"13","author":"Takabatake","year":"2008","journal-title":"Nephrology"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"44904","DOI":"10.1038\/srep44904","article-title":"Kidney-specific transposon-mediated gene transfer in vivo","volume":"7","author":"Woodard","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"306","DOI":"10.1023\/A:1007501122611","article-title":"In vivo gene delivery to the liver using novel galactosylated cationic liposomes","volume":"17","author":"Kawakami","year":"2000","journal-title":"Pharm. Res."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"481","DOI":"10.1538\/expanim.60.481","article-title":"Effect of three types of mixed anesthetic agents alternate to ketamine in mice","volume":"60","author":"Kawai","year":"2011","journal-title":"Exp. Anim."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"2745","DOI":"10.1093\/ndt\/gfl327","article-title":"Targeting of interstitial cells using a simple gene-transfer strategy","volume":"21","author":"Fujii","year":"2006","journal-title":"Nephrol. Dial. Transplant."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1518","DOI":"10.1038\/nn.4107","article-title":"ScaleS: An optical clearing palette for biological imaging","volume":"18","author":"Hama","year":"2015","journal-title":"Nat. Neurosci."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"997","DOI":"10.1292\/jvms.57.997","article-title":"Renal responses to atrial natriuretic peptide (ANP) in rats with non-oliguric acute renal failure induced by cisplatin","volume":"57","author":"Nagano","year":"1995","journal-title":"J. Vet. Med. Sci."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1002\/path.1711180307","article-title":"Renal damage caused by gentamicin: A study of the effects on renal morphology and urinary enzyme excretion","volume":"118","author":"Wellwood","year":"1976","journal-title":"J. Pathol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1093\/toxsci\/kfm260","article-title":"Comparison of kidney injury molecule-1 and other nephrotoxicity biomarkers in urine and kidney following acute exposure to gentamicin, mercury, and chromium","volume":"101","author":"Zhou","year":"2008","journal-title":"Toxicol. Sci."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1551","DOI":"10.1038\/sj.gt.3302569","article-title":"Direct electrotransfer of hHGF gene into kidney ameliorates ischemic acute renal failure","volume":"12","author":"Franquesa","year":"2005","journal-title":"Gene Ther."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"944","DOI":"10.1248\/bpb.b18-00094","article-title":"Determining Transgene Expression Characteristics Using a Suction Device with Multiple Hole Adjusting a Left Lateral Lobe of the Mouse Liver","volume":"41","author":"Haraguchi","year":"2018","journal-title":"Biol. Pharm. Bull."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1627","DOI":"10.1248\/bpb.33.1627","article-title":"Key physiological phenomena governing transgene expression based on tissue pressure-mediated transfection in mice","volume":"33","author":"Mukai","year":"2010","journal-title":"Biol. Pharm. Bull."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1320","DOI":"10.1172\/JCI1694","article-title":"Correction of renal tubular acidosis in carbonic anhydrase II-deficient mice with gene therapy","volume":"101","author":"Lai","year":"1998","journal-title":"J. Clin. Investig."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1159\/000333071","article-title":"Adeno-Associated Virus-Mediated Gene Transfer to Renal Tubule Cells via a Retrograde Ureteral Approach","volume":"1","author":"Chung","year":"2011","journal-title":"Nephron Extra"},{"key":"ref_30","first-page":"e56324","article-title":"Hydrodynamic Renal Pelvis Injection for Non-viral Expression of Proteins in the Kidney","volume":"131","author":"Woodard","year":"2018","journal-title":"J. Vis. Exp."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"229","DOI":"10.1007\/s10157-006-0442-7","article-title":"Gene therapy targeting kidney diseases: Routes and vehicles","volume":"10","author":"Isaka","year":"2006","journal-title":"Clin. Exp. Nephrol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"164","DOI":"10.1089\/biores.2014.0057","article-title":"Gene-Activated Matrix Comprised of Atelocollagen and Plasmid DNA Encoding BMP4 or Runx2 Promotes Rat Cranial Bone Augmentation","volume":"4","author":"Umebayashi","year":"2015","journal-title":"Biores. Open Access"},{"key":"ref_33","first-page":"140","article-title":"Transfection of human HGF plasmid DNA improves limb salvage in Buerger\u2019s disease patients with critical limb ischemia","volume":"30","author":"Shigematsu","year":"2011","journal-title":"Int. Angiol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"494","DOI":"10.1016\/j.ejvs.2015.05.007","article-title":"Clinical Safety and Preliminary Efficacy of Plasmid pUDK-HGF Expressing Human Hepatocyte Growth Factor (HGF) in Patients with Critical Limb Ischemia","volume":"50","author":"Cui","year":"2015","journal-title":"Eur. J. Vasc. Endovasc. Surg."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1681\/ASN.2005111187","article-title":"Inhibition of histone deacetylase activity suppresses epithelial-to-mesenchymal transition induced by TGF-beta1 in human renal epithelial cells","volume":"18","author":"Yoshikawa","year":"2007","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1047","DOI":"10.1038\/nm.3218","article-title":"Origin and function of myofibroblasts in kidney fibrosis","volume":"19","author":"LeBleu","year":"2013","journal-title":"Nat. Med."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"427","DOI":"10.3109\/1061186X.2014.1002788","article-title":"Long-term in vivo gene expression in mouse kidney using \u03c6C31 integrase and electroporation","volume":"23","author":"Otani","year":"2015","journal-title":"J. Drug Target"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"2464","DOI":"10.1097\/01.ASN.0000031827.16102.C1","article-title":"Hepatocyte growth factor gene therapy and angiotensin II blockade synergistically attenuate renal interstitial fibrosis in mice","volume":"13","author":"Yang","year":"2002","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"8655","DOI":"10.1074\/jbc.M110.174037","article-title":"Klotho inhibits transforming growth factor-beta1 (TGF-beta1) signaling and suppresses renal fibrosis and cancer metastasis in mice","volume":"286","author":"Doi","year":"2011","journal-title":"J. Biol. Chem."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1345","DOI":"10.1007\/s10157-019-01783-w","article-title":"rAAV6-mediated miR-29b delivery suppresses renal fibrosis","volume":"23","author":"Saito","year":"2019","journal-title":"Clin. Exp. Nephrol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"759","DOI":"10.1038\/nrd4278","article-title":"mRNA-based therapeutics\u2014Developing a new class of drugs","volume":"13","author":"Sahin","year":"2014","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Uchida, S., Itaka, K., Uchida, H., Hayakawa, K., Ogata, T., Ishii, T., Fukushima, S., Osada, K., and Kataoka, K. (2013). In vivo messenger RNA introduction into the central nervous system using polyplex nanomicelle. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0056220"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1337","DOI":"10.1517\/14712598.2015.1057563","article-title":"Modified mRNA as an alternative to plasmid DNA (pDNA) for transcript replacement and vaccination therapy","volume":"15","author":"Youn","year":"2015","journal-title":"Expert. Opin. Biol. Ther."}],"container-title":["Pharmaceutics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1999-4923\/12\/2\/114\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T08:53:37Z","timestamp":1760172817000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1999-4923\/12\/2\/114"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,2,1]]},"references-count":43,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2020,2]]}},"alternative-id":["pharmaceutics12020114"],"URL":"https:\/\/doi.org\/10.3390\/pharmaceutics12020114","relation":{},"ISSN":["1999-4923"],"issn-type":[{"value":"1999-4923","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,2,1]]}}}