Application of ultrasound elastography for monitoring the effects of TβR1 shRNA therapy on hepatic fibrosis in a rat model
Background To investigate the application of ultrasound elastography in monitoring the effects of the transforming growth factor (TGF)-β1 signaling pathway-targeted combination therapy for hepatic fibrosis. Methods 1. Short hairpin RNA (shRNA) constructs targeted towards TβR1 were designed, synthesi...
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| description | Background To investigate the application of ultrasound elastography in monitoring the effects of the transforming growth factor (TGF)-β1 signaling pathway-targeted combination therapy for hepatic fibrosis. Methods 1. Short hairpin RNA (shRNA) constructs targeted towards TβR1 were designed, synthesized, and packaged using an adeno-associated virus (AAV), and the effective target shRNA was selected based on transfection results. 2. Fifty rats were randomly allocated (n = 10 per group) to the (A) control group, (B) model group, (C) 0-week therapy group, (D) 4-week therapy group, and (E) combination therapy group. At weeks 2, 4, 6, 8, 10, and 12, acoustic radiation force impulse (ARFI) elastography was used to measure the liver stiffness, inner diameter of the portal vein diameter, and blood velocity; radio frequency ultrasound imaging was used to measure the abdominal aortic elasticity parameter and pulse wave velocity (PWV) of the rats. 3. At week 12, portal vein puncture was performed to measure the portal venous pressure, and rat liver specimens were obtained for the pathological measurement of the degree of hepatic fibrosis. Results 1. An shRNA interference sequence targeted towards TβR1 was successfully designed, screened, and packaged using an AAV, and small-animal imaging results indicated expression of the specific shRNA in the liver. 2. At week 12, the ultrasound elastography results were significantly different between the experimental groups and the control group (p < 0.01); among the experimental groups, differences were significant between the therapy groups and the model group (p < 0.01). For groups C and E, the therapeutic effects on hepatic fibrosis in rats were significant, with the pathological results indicating a significant reduction in the degree of hepatic fibrosis (p < 0.01). The therapeutic effectiveness of group D was less than that of group C (p < 0.05). Significant differences existed between the portal venous pressure of the experimental groups and of the control group (p < 0.01). For the abdominal aortic elasticity parameter measured by radio frequency ultrasound imaging, differences existed between the values obtained from the experimental groups and from that of the control group (p < 0.05), while statistically significant differences were not found among the various experimental groups. 3. Continuous ultrasound examination results indicated that the elasticity value of group A was significantly different from those of the oth |
| doi_str_mv | 10.1371/journal.pone.0253150 |
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| fullrecord | <record><control><sourceid>proquest_plos_</sourceid><recordid>TN_cdi_plos_journals_2545974216</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><doaj_id>oai_doaj_org_article_85164990024f474391c294419d8db895</doaj_id><sourcerecordid>2545974216</sourcerecordid><originalsourceid>FETCH-LOGICAL-c452t-2a44eed4b4bc2afbe54b58f063578bf2127d4ad8faa8675c86fc689d6b101f803</originalsourceid><addsrcrecordid>eNp1ksuKFDEUhgtRnHH0DQQDrrvNvVIboRm8DAwKw7gOuXalqa6USUpofCsfxGcyZZfiLFwl5Pz_d05-TtO8RHCLSIveHOKcRjVspzi6LcSMIAYfNZeoI3jDMSSP_7lfNM9yPkDIiOD8aXNBKBKIt_Cy-b6bpiEYVUIcQfRgHkpSOc6jBW5QucR9UlN_Aj4mcIxjKDGFcQ9K74Dz3pmSF9f9zx93COT-7tNuKVXLCVRe76YKNsAHnWIOGYQRKJBUqSjrhufNE6-G7F6s51Xz5f27--uPm9vPH26ud7cbQxkuG6wodc5STbXBymvHqGbCQ05YK7THCLeWKiu8UoK3zAjuDRed5RpB5AUkV82rM3caYpZrblliRlnXUox4VdycFTaqg5xSOKp0klEF-fshpr1Uqf5kcFIwxGnXQYippy0lHTK4oxR1VlgtOlZZb9dusz46a9xYEx0eQB9WxtDLffwmBSYCiQXwegWk-HV2ufxnZHpWmRptTs7_7YCgXBbkj0suCyLXBSG_AOQxsYg</addsrcrecordid><sourcetype>Open Website</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2545974216</pqid></control><display><type>article</type><title>Application of ultrasound elastography for monitoring the effects of TβR1 shRNA therapy on hepatic fibrosis in a rat model</title><source>Public Library of Science (PLoS) Journals Open Access</source><source>DOAJ Directory of Open Access Journals</source><source>Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals</source><source>PubMed Central</source><source>Free Full-Text Journals in Chemistry</source><creator>Shi, Xiangzhou ; Li, Jinghua ; Min, Binying ; Yang, Ruijing ; He, Chunxiang ; Yang, Yilin</creator><creatorcontrib>Shi, Xiangzhou ; Li, Jinghua ; Min, Binying ; Yang, Ruijing ; He, Chunxiang ; Yang, Yilin</creatorcontrib><description><![CDATA[Background To investigate the application of ultrasound elastography in monitoring the effects of the transforming growth factor (TGF)-β1 signaling pathway-targeted combination therapy for hepatic fibrosis. Methods 1. Short hairpin RNA (shRNA) constructs targeted towards TβR1 were designed, synthesized, and packaged using an adeno-associated virus (AAV), and the effective target shRNA was selected based on transfection results. 2. Fifty rats were randomly allocated (n = 10 per group) to the (A) control group, (B) model group, (C) 0-week therapy group, (D) 4-week therapy group, and (E) combination therapy group. At weeks 2, 4, 6, 8, 10, and 12, acoustic radiation force impulse (ARFI) elastography was used to measure the liver stiffness, inner diameter of the portal vein diameter, and blood velocity; radio frequency ultrasound imaging was used to measure the abdominal aortic elasticity parameter and pulse wave velocity (PWV) of the rats. 3. At week 12, portal vein puncture was performed to measure the portal venous pressure, and rat liver specimens were obtained for the pathological measurement of the degree of hepatic fibrosis. Results 1. An shRNA interference sequence targeted towards TβR1 was successfully designed, screened, and packaged using an AAV, and small-animal imaging results indicated expression of the specific shRNA in the liver. 2. At week 12, the ultrasound elastography results were significantly different between the experimental groups and the control group (p < 0.01); among the experimental groups, differences were significant between the therapy groups and the model group (p < 0.01). For groups C and E, the therapeutic effects on hepatic fibrosis in rats were significant, with the pathological results indicating a significant reduction in the degree of hepatic fibrosis (p < 0.01). The therapeutic effectiveness of group D was less than that of group C (p < 0.05). Significant differences existed between the portal venous pressure of the experimental groups and of the control group (p < 0.01). For the abdominal aortic elasticity parameter measured by radio frequency ultrasound imaging, differences existed between the values obtained from the experimental groups and from that of the control group (p < 0.05), while statistically significant differences were not found among the various experimental groups. 3. Continuous ultrasound examination results indicated that the elasticity value of group A was significantly different from those of the other groups after 2 weeks of model establishment (p < 0.01); after 6 weeks, the elasticity values of groups C and E were significantly different compared with those of groups B and D (p < 0.01). For the abdominal aortic elasticity parameter and pulse wave velocity (PWV), there were no significant differences among the various groups (p > 0.05). Conclusion CCl4-induced hepatic fibrosis can be treated through shRNA silencing of TβR1. Ultrasound ARFI elastography is superior to external force-assisted elastography as it can reflect the degree of fibrosis in moderate to severe hepatic fibrosis and the variations in the degree of fibrosis after treatment. Portal venous pressure was positively correlated with the degree of fibrosis; with early combination therapy, both the degree of fibrosis and portal venous pressure could be effectively reduced.]]></description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0253150</identifier><identifier>PMID: 34181670</identifier><language>eng</language><publisher>San Francisco: Public Library of Science</publisher><subject>Animals ; Aorta ; Auroral kilometric radiation ; Biology and Life Sciences ; Carbon tetrachloride ; Diameters ; Elasticity ; Experiments ; Fibrosis ; Growth factors ; Imaging ; Laboratories ; Liver ; Liver diseases ; Mathematical models ; Medical research ; Medicine and Health Sciences ; Monitoring ; Parameters ; Portal vein ; Pressure ; Radiation ; Research and Analysis Methods ; Signal transduction ; Sound waves ; Statistical analysis ; Stiffness ; Therapy ; Transfection ; Ultrasonic imaging ; Ultrasound ; Veins ; Veins & arteries ; Velocity ; Viruses ; Wave velocity</subject><ispartof>PloS one, 2021-06, Vol.16 (6), p.e0253150</ispartof><rights>2021 Shi et al. This is an open access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2021 Shi et al 2021 Shi et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><cites>FETCH-LOGICAL-c452t-2a44eed4b4bc2afbe54b58f063578bf2127d4ad8faa8675c86fc689d6b101f803</cites><orcidid>0000-0002-4527-1854</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC8238185/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC8238185/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,2096,2915,23845,27901,27902,53766,53768,79569,79570</link.rule.ids></links><search><creatorcontrib>Shi, Xiangzhou</creatorcontrib><creatorcontrib>Li, Jinghua</creatorcontrib><creatorcontrib>Min, Binying</creatorcontrib><creatorcontrib>Yang, Ruijing</creatorcontrib><creatorcontrib>He, Chunxiang</creatorcontrib><creatorcontrib>Yang, Yilin</creatorcontrib><title>Application of ultrasound elastography for monitoring the effects of TβR1 shRNA therapy on hepatic fibrosis in a rat model</title><title>PloS one</title><description><![CDATA[Background To investigate the application of ultrasound elastography in monitoring the effects of the transforming growth factor (TGF)-β1 signaling pathway-targeted combination therapy for hepatic fibrosis. Methods 1. Short hairpin RNA (shRNA) constructs targeted towards TβR1 were designed, synthesized, and packaged using an adeno-associated virus (AAV), and the effective target shRNA was selected based on transfection results. 2. Fifty rats were randomly allocated (n = 10 per group) to the (A) control group, (B) model group, (C) 0-week therapy group, (D) 4-week therapy group, and (E) combination therapy group. At weeks 2, 4, 6, 8, 10, and 12, acoustic radiation force impulse (ARFI) elastography was used to measure the liver stiffness, inner diameter of the portal vein diameter, and blood velocity; radio frequency ultrasound imaging was used to measure the abdominal aortic elasticity parameter and pulse wave velocity (PWV) of the rats. 3. At week 12, portal vein puncture was performed to measure the portal venous pressure, and rat liver specimens were obtained for the pathological measurement of the degree of hepatic fibrosis. Results 1. An shRNA interference sequence targeted towards TβR1 was successfully designed, screened, and packaged using an AAV, and small-animal imaging results indicated expression of the specific shRNA in the liver. 2. At week 12, the ultrasound elastography results were significantly different between the experimental groups and the control group (p < 0.01); among the experimental groups, differences were significant between the therapy groups and the model group (p < 0.01). For groups C and E, the therapeutic effects on hepatic fibrosis in rats were significant, with the pathological results indicating a significant reduction in the degree of hepatic fibrosis (p < 0.01). The therapeutic effectiveness of group D was less than that of group C (p < 0.05). Significant differences existed between the portal venous pressure of the experimental groups and of the control group (p < 0.01). For the abdominal aortic elasticity parameter measured by radio frequency ultrasound imaging, differences existed between the values obtained from the experimental groups and from that of the control group (p < 0.05), while statistically significant differences were not found among the various experimental groups. 3. Continuous ultrasound examination results indicated that the elasticity value of group A was significantly different from those of the other groups after 2 weeks of model establishment (p < 0.01); after 6 weeks, the elasticity values of groups C and E were significantly different compared with those of groups B and D (p < 0.01). For the abdominal aortic elasticity parameter and pulse wave velocity (PWV), there were no significant differences among the various groups (p > 0.05). Conclusion CCl4-induced hepatic fibrosis can be treated through shRNA silencing of TβR1. Ultrasound ARFI elastography is superior to external force-assisted elastography as it can reflect the degree of fibrosis in moderate to severe hepatic fibrosis and the variations in the degree of fibrosis after treatment. Portal venous pressure was positively correlated with the degree of fibrosis; with early combination therapy, both the degree of fibrosis and portal venous pressure could be effectively reduced.]]></description><subject>Animals</subject><subject>Aorta</subject><subject>Auroral kilometric radiation</subject><subject>Biology and Life Sciences</subject><subject>Carbon tetrachloride</subject><subject>Diameters</subject><subject>Elasticity</subject><subject>Experiments</subject><subject>Fibrosis</subject><subject>Growth factors</subject><subject>Imaging</subject><subject>Laboratories</subject><subject>Liver</subject><subject>Liver diseases</subject><subject>Mathematical models</subject><subject>Medical research</subject><subject>Medicine and Health Sciences</subject><subject>Monitoring</subject><subject>Parameters</subject><subject>Portal vein</subject><subject>Pressure</subject><subject>Radiation</subject><subject>Research and Analysis Methods</subject><subject>Signal transduction</subject><subject>Sound waves</subject><subject>Statistical analysis</subject><subject>Stiffness</subject><subject>Therapy</subject><subject>Transfection</subject><subject>Ultrasonic imaging</subject><subject>Ultrasound</subject><subject>Veins</subject><subject>Veins & arteries</subject><subject>Velocity</subject><subject>Viruses</subject><subject>Wave velocity</subject><issn>1932-6203</issn><issn>1932-6203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2021</creationdate><recordtype>article</recordtype><sourceid>BENPR</sourceid><sourceid>DOA</sourceid><recordid>eNp1ksuKFDEUhgtRnHH0DQQDrrvNvVIboRm8DAwKw7gOuXalqa6USUpofCsfxGcyZZfiLFwl5Pz_d05-TtO8RHCLSIveHOKcRjVspzi6LcSMIAYfNZeoI3jDMSSP_7lfNM9yPkDIiOD8aXNBKBKIt_Cy-b6bpiEYVUIcQfRgHkpSOc6jBW5QucR9UlN_Aj4mcIxjKDGFcQ9K74Dz3pmSF9f9zx93COT-7tNuKVXLCVRe76YKNsAHnWIOGYQRKJBUqSjrhufNE6-G7F6s51Xz5f27--uPm9vPH26ud7cbQxkuG6wodc5STbXBymvHqGbCQ05YK7THCLeWKiu8UoK3zAjuDRed5RpB5AUkV82rM3caYpZrblliRlnXUox4VdycFTaqg5xSOKp0klEF-fshpr1Uqf5kcFIwxGnXQYippy0lHTK4oxR1VlgtOlZZb9dusz46a9xYEx0eQB9WxtDLffwmBSYCiQXwegWk-HV2ufxnZHpWmRptTs7_7YCgXBbkj0suCyLXBSG_AOQxsYg</recordid><startdate>20210628</startdate><enddate>20210628</enddate><creator>Shi, Xiangzhou</creator><creator>Li, Jinghua</creator><creator>Min, Binying</creator><creator>Yang, Ruijing</creator><creator>He, Chunxiang</creator><creator>Yang, Yilin</creator><general>Public Library of Science</general><general>Public Library of Science 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of ultrasound elastography for monitoring the effects of TβR1 shRNA therapy on hepatic fibrosis in a rat model</title><author>Shi, Xiangzhou ; Li, Jinghua ; Min, Binying ; Yang, Ruijing ; He, Chunxiang ; Yang, Yilin</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c452t-2a44eed4b4bc2afbe54b58f063578bf2127d4ad8faa8675c86fc689d6b101f803</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2021</creationdate><topic>Animals</topic><topic>Aorta</topic><topic>Auroral kilometric radiation</topic><topic>Biology and Life Sciences</topic><topic>Carbon tetrachloride</topic><topic>Diameters</topic><topic>Elasticity</topic><topic>Experiments</topic><topic>Fibrosis</topic><topic>Growth factors</topic><topic>Imaging</topic><topic>Laboratories</topic><topic>Liver</topic><topic>Liver diseases</topic><topic>Mathematical models</topic><topic>Medical research</topic><topic>Medicine and Health Sciences</topic><topic>Monitoring</topic><topic>Parameters</topic><topic>Portal vein</topic><topic>Pressure</topic><topic>Radiation</topic><topic>Research and Analysis Methods</topic><topic>Signal transduction</topic><topic>Sound waves</topic><topic>Statistical analysis</topic><topic>Stiffness</topic><topic>Therapy</topic><topic>Transfection</topic><topic>Ultrasonic imaging</topic><topic>Ultrasound</topic><topic>Veins</topic><topic>Veins & arteries</topic><topic>Velocity</topic><topic>Viruses</topic><topic>Wave velocity</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Shi, Xiangzhou</creatorcontrib><creatorcontrib>Li, Jinghua</creatorcontrib><creatorcontrib>Min, Binying</creatorcontrib><creatorcontrib>Yang, Ruijing</creatorcontrib><creatorcontrib>He, Chunxiang</creatorcontrib><creatorcontrib>Yang, Yilin</creatorcontrib><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Animal Behavior 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Abstracts</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>PloS one</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Shi, Xiangzhou</au><au>Li, Jinghua</au><au>Min, Binying</au><au>Yang, Ruijing</au><au>He, Chunxiang</au><au>Yang, Yilin</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Application of ultrasound elastography for monitoring the effects of TβR1 shRNA therapy on hepatic fibrosis in a rat model</atitle><jtitle>PloS one</jtitle><date>2021-06-28</date><risdate>2021</risdate><volume>16</volume><issue>6</issue><spage>e0253150</spage><pages>e0253150-</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract><![CDATA[Background To investigate the application of ultrasound elastography in monitoring the effects of the transforming growth factor (TGF)-β1 signaling pathway-targeted combination therapy for hepatic fibrosis. Methods 1. Short hairpin RNA (shRNA) constructs targeted towards TβR1 were designed, synthesized, and packaged using an adeno-associated virus (AAV), and the effective target shRNA was selected based on transfection results. 2. Fifty rats were randomly allocated (n = 10 per group) to the (A) control group, (B) model group, (C) 0-week therapy group, (D) 4-week therapy group, and (E) combination therapy group. At weeks 2, 4, 6, 8, 10, and 12, acoustic radiation force impulse (ARFI) elastography was used to measure the liver stiffness, inner diameter of the portal vein diameter, and blood velocity; radio frequency ultrasound imaging was used to measure the abdominal aortic elasticity parameter and pulse wave velocity (PWV) of the rats. 3. At week 12, portal vein puncture was performed to measure the portal venous pressure, and rat liver specimens were obtained for the pathological measurement of the degree of hepatic fibrosis. Results 1. An shRNA interference sequence targeted towards TβR1 was successfully designed, screened, and packaged using an AAV, and small-animal imaging results indicated expression of the specific shRNA in the liver. 2. At week 12, the ultrasound elastography results were significantly different between the experimental groups and the control group (p < 0.01); among the experimental groups, differences were significant between the therapy groups and the model group (p < 0.01). For groups C and E, the therapeutic effects on hepatic fibrosis in rats were significant, with the pathological results indicating a significant reduction in the degree of hepatic fibrosis (p < 0.01). The therapeutic effectiveness of group D was less than that of group C (p < 0.05). Significant differences existed between the portal venous pressure of the experimental groups and of the control group (p < 0.01). For the abdominal aortic elasticity parameter measured by radio frequency ultrasound imaging, differences existed between the values obtained from the experimental groups and from that of the control group (p < 0.05), while statistically significant differences were not found among the various experimental groups. 3. Continuous ultrasound examination results indicated that the elasticity value of group A was significantly different from those of the other groups after 2 weeks of model establishment (p < 0.01); after 6 weeks, the elasticity values of groups C and E were significantly different compared with those of groups B and D (p < 0.01). For the abdominal aortic elasticity parameter and pulse wave velocity (PWV), there were no significant differences among the various groups (p > 0.05). Conclusion CCl4-induced hepatic fibrosis can be treated through shRNA silencing of TβR1. Ultrasound ARFI elastography is superior to external force-assisted elastography as it can reflect the degree of fibrosis in moderate to severe hepatic fibrosis and the variations in the degree of fibrosis after treatment. Portal venous pressure was positively correlated with the degree of fibrosis; with early combination therapy, both the degree of fibrosis and portal venous pressure could be effectively reduced.]]></abstract><cop>San Francisco</cop><pub>Public Library of Science</pub><pmid>34181670</pmid><doi>10.1371/journal.pone.0253150</doi><orcidid>https://orcid.org/0000-0002-4527-1854</orcidid><oa>free_for_read</oa></addata></record> |
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| subjects | Animals Aorta Auroral kilometric radiation Biology and Life Sciences Carbon tetrachloride Diameters Elasticity Experiments Fibrosis Growth factors Imaging Laboratories Liver Liver diseases Mathematical models Medical research Medicine and Health Sciences Monitoring Parameters Portal vein Pressure Radiation Research and Analysis Methods Signal transduction Sound waves Statistical analysis Stiffness Therapy Transfection Ultrasonic imaging Ultrasound Veins Veins & arteries Velocity Viruses Wave velocity |
| title | Application of ultrasound elastography for monitoring the effects of TβR1 shRNA therapy on hepatic fibrosis in a rat model |
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