The Rho kinase signaling pathway participates in tubular mitochondrial oxidative injury and apoptosis in uric acid nephropathy
Introduction Oxidative stress is a pathologic feature of hyperuricemia that is highly prevalent and that contributes to kidney tubular interstitial fibrosis. Rho-kinase is closely related to mitochondrial-induced oxidative stress. Herein, we designed a study to explore the expression and role of Rho...
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| Veröffentlicht in: | Journal of international medical research 2021-06, Vol.49 (6), p.3000605211021752-3000605211021752 |
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| creator | Su, Yan Hu, Langtao Wang, Yanni Ying, Gangqiang Ma, Chunyang Wei, Jiali |
| description | Introduction
Oxidative stress is a pathologic feature of hyperuricemia that is highly prevalent and that contributes to kidney tubular interstitial fibrosis. Rho-kinase is closely related to mitochondrial-induced oxidative stress. Herein, we designed a study to explore the expression and role of Rho-kinase in hyperuricemia nephropathy. The secondary objective was to investigate whether the Rho-kinase signaling pathway regulates hyperuricemic tubular oxidative injury and apoptosis via the mitochondrial pathway in addition to the mechanisms that are involved.
Materials and methods
HK-2 cells were divided into the following five groups: normal; uric acid (UA); UA+Fasudil; UA+ROCK1 si-RNA; and UA+sc-siRNA. Rho-kinase activity, mitochondrial oxidative injury, and apoptosis-related protein levels were measured in each group. A t-test was used to analyze the difference between groups.
Results
Myosin phosphatase target subunit 1 (MYPT1) overexpression was shown in HK-2 cells, which was caused by UA. High concentrations of UA also up-regulated Rho-kinase expression and mitochondrial and apoptosis-related protein expression, while treatment with fasudil and ROCK1 si-RNA significantly attenuated these responses.
Conclusion
The Rho-kinase signaling pathway participates in tubular mitochondrial oxidative injury and apoptosis via regulating mitochondrial dyneins/biogenic genes in UA nephropathy, which suggests that the mitochondrial pathway might be a potential therapeutic target for hyperuricemia nephropathy. |
| doi_str_mv | 10.1177/03000605211021752 |
| format | Article |
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Oxidative stress is a pathologic feature of hyperuricemia that is highly prevalent and that contributes to kidney tubular interstitial fibrosis. Rho-kinase is closely related to mitochondrial-induced oxidative stress. Herein, we designed a study to explore the expression and role of Rho-kinase in hyperuricemia nephropathy. The secondary objective was to investigate whether the Rho-kinase signaling pathway regulates hyperuricemic tubular oxidative injury and apoptosis via the mitochondrial pathway in addition to the mechanisms that are involved.
Materials and methods
HK-2 cells were divided into the following five groups: normal; uric acid (UA); UA+Fasudil; UA+ROCK1 si-RNA; and UA+sc-siRNA. Rho-kinase activity, mitochondrial oxidative injury, and apoptosis-related protein levels were measured in each group. A t-test was used to analyze the difference between groups.
Results
Myosin phosphatase target subunit 1 (MYPT1) overexpression was shown in HK-2 cells, which was caused by UA. High concentrations of UA also up-regulated Rho-kinase expression and mitochondrial and apoptosis-related protein expression, while treatment with fasudil and ROCK1 si-RNA significantly attenuated these responses.
Conclusion
The Rho-kinase signaling pathway participates in tubular mitochondrial oxidative injury and apoptosis via regulating mitochondrial dyneins/biogenic genes in UA nephropathy, which suggests that the mitochondrial pathway might be a potential therapeutic target for hyperuricemia nephropathy.</description><identifier>ISSN: 0300-0605</identifier><identifier>EISSN: 1473-2300</identifier><identifier>DOI: 10.1177/03000605211021752</identifier><identifier>PMID: 34167354</identifier><language>eng</language><publisher>London, England: SAGE Publications</publisher><subject>Apoptosis ; Cell Line ; Humans ; Kidney Diseases ; Kinases ; Mitochondria - pathology ; Oxidative Stress ; Pre-Clinical Research Report ; rho-Associated Kinases - genetics ; Signal Transduction ; Uric Acid</subject><ispartof>Journal of international medical research, 2021-06, Vol.49 (6), p.3000605211021752-3000605211021752</ispartof><rights>The Author(s) 2021</rights><rights>The Author(s) 2021. This work is licensed under the Creative Commons Attribution – Non-Commercial License https://creativecommons.org/licenses/by-nc/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>The Author(s) 2021 2021 SAGE Publications</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c532t-8432c46a6ca88d9b078d4181a0d2f91848eec788a32e223a6a422ec5cc0a8d6e3</citedby><cites>FETCH-LOGICAL-c532t-8432c46a6ca88d9b078d4181a0d2f91848eec788a32e223a6a422ec5cc0a8d6e3</cites><orcidid>0000-0002-7546-6388</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/PMC8236795/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC8236795/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,864,885,2102,21966,27853,27924,27925,44945,45333,53791,53793</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/34167354$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Su, Yan</creatorcontrib><creatorcontrib>Hu, Langtao</creatorcontrib><creatorcontrib>Wang, Yanni</creatorcontrib><creatorcontrib>Ying, Gangqiang</creatorcontrib><creatorcontrib>Ma, Chunyang</creatorcontrib><creatorcontrib>Wei, Jiali</creatorcontrib><title>The Rho kinase signaling pathway participates in tubular mitochondrial oxidative injury and apoptosis in uric acid nephropathy</title><title>Journal of international medical research</title><addtitle>J Int Med Res</addtitle><description>Introduction
Oxidative stress is a pathologic feature of hyperuricemia that is highly prevalent and that contributes to kidney tubular interstitial fibrosis. Rho-kinase is closely related to mitochondrial-induced oxidative stress. Herein, we designed a study to explore the expression and role of Rho-kinase in hyperuricemia nephropathy. The secondary objective was to investigate whether the Rho-kinase signaling pathway regulates hyperuricemic tubular oxidative injury and apoptosis via the mitochondrial pathway in addition to the mechanisms that are involved.
Materials and methods
HK-2 cells were divided into the following five groups: normal; uric acid (UA); UA+Fasudil; UA+ROCK1 si-RNA; and UA+sc-siRNA. Rho-kinase activity, mitochondrial oxidative injury, and apoptosis-related protein levels were measured in each group. A t-test was used to analyze the difference between groups.
Results
Myosin phosphatase target subunit 1 (MYPT1) overexpression was shown in HK-2 cells, which was caused by UA. High concentrations of UA also up-regulated Rho-kinase expression and mitochondrial and apoptosis-related protein expression, while treatment with fasudil and ROCK1 si-RNA significantly attenuated these responses.
Conclusion
The Rho-kinase signaling pathway participates in tubular mitochondrial oxidative injury and apoptosis via regulating mitochondrial dyneins/biogenic genes in UA nephropathy, which suggests that the mitochondrial pathway might be a potential therapeutic target for hyperuricemia nephropathy.</description><subject>Apoptosis</subject><subject>Cell Line</subject><subject>Humans</subject><subject>Kidney Diseases</subject><subject>Kinases</subject><subject>Mitochondria - pathology</subject><subject>Oxidative Stress</subject><subject>Pre-Clinical Research Report</subject><subject>rho-Associated Kinases - genetics</subject><subject>Signal Transduction</subject><subject>Uric Acid</subject><issn>0300-0605</issn><issn>1473-2300</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2021</creationdate><recordtype>article</recordtype><sourceid>AFRWT</sourceid><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>DOA</sourceid><recordid>eNp1kktv1DAQgCMEokvhB3BBlrhwSfHbzgUJVTwqVUJC5WxNbG_iJRsHO2nZC78d724pFMRpZM8333jkqarnBJ8RotRrzDDGEgtKCKZECfqgWhGuWE1L4mG12ufrPXBSPcl5gzGnUtDH1QnjRCom-Kr6cdV79LmP6GsYIXuUQzfCEMYOTTD3N7ArMc3BhnL0GYURzUu7DJDQNszR9nF0KcCA4vfgYA7XviCbJe0QjA7BFKc55nCoW1KwCGxwaPRTn-Lev3taPVrDkP2z23hafXn_7ur8Y3356cPF-dvL2gpG51pzRi2XIC1o7ZoWK-040QSwo-uGaK69t0prYNRTykACp9RbYS0G7aRnp9XF0esibMyUwhbSzkQI5nARU2cOYw7eSAUtbSmAVYw7gRuF_doqah13VAtdXG-Ormlpt95ZP84JhnvS-5kx9KaL10ZTJlUjiuDVrSDFb4vPs9mGbP0wwOjjkg0VXEisdSML-vIvdBOXVH7oQMkGK8xoociRsinmnPz67jEEm_2mmH82pdS8-HOKu4pfq1GAsyOQofO_2_7f-BO_r8hi</recordid><startdate>20210601</startdate><enddate>20210601</enddate><creator>Su, Yan</creator><creator>Hu, Langtao</creator><creator>Wang, Yanni</creator><creator>Ying, Gangqiang</creator><creator>Ma, Chunyang</creator><creator>Wei, Jiali</creator><general>SAGE Publications</general><general>Sage Publications Ltd</general><general>SAGE Publishing</general><scope>AFRWT</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7X7</scope><scope>7XB</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>K9.</scope><scope>M0S</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>7X8</scope><scope>5PM</scope><scope>DOA</scope><orcidid>https://orcid.org/0000-0002-7546-6388</orcidid></search><sort><creationdate>20210601</creationdate><title>The Rho kinase signaling pathway participates in tubular mitochondrial oxidative injury and apoptosis in uric acid nephropathy</title><author>Su, Yan ; Hu, Langtao ; Wang, Yanni ; Ying, Gangqiang ; Ma, Chunyang ; Wei, Jiali</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c532t-8432c46a6ca88d9b078d4181a0d2f91848eec788a32e223a6a422ec5cc0a8d6e3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2021</creationdate><topic>Apoptosis</topic><topic>Cell Line</topic><topic>Humans</topic><topic>Kidney Diseases</topic><topic>Kinases</topic><topic>Mitochondria - pathology</topic><topic>Oxidative Stress</topic><topic>Pre-Clinical Research Report</topic><topic>rho-Associated Kinases - genetics</topic><topic>Signal Transduction</topic><topic>Uric Acid</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Su, Yan</creatorcontrib><creatorcontrib>Hu, Langtao</creatorcontrib><creatorcontrib>Wang, Yanni</creatorcontrib><creatorcontrib>Ying, Gangqiang</creatorcontrib><creatorcontrib>Ma, Chunyang</creatorcontrib><creatorcontrib>Wei, Jiali</creatorcontrib><collection>SAGE Open Access</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>ProQuest - Health & Medical Complete保健、医学与药学数据库</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>ProQuest Central</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Publicly Available Content Database (Proquest) (PQ_SDU_P3)</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>Journal of international medical research</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Su, Yan</au><au>Hu, Langtao</au><au>Wang, Yanni</au><au>Ying, Gangqiang</au><au>Ma, Chunyang</au><au>Wei, Jiali</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>The Rho kinase signaling pathway participates in tubular mitochondrial oxidative injury and apoptosis in uric acid nephropathy</atitle><jtitle>Journal of international medical research</jtitle><addtitle>J Int Med Res</addtitle><date>2021-06-01</date><risdate>2021</risdate><volume>49</volume><issue>6</issue><spage>3000605211021752</spage><epage>3000605211021752</epage><pages>3000605211021752-3000605211021752</pages><issn>0300-0605</issn><eissn>1473-2300</eissn><abstract>Introduction
Oxidative stress is a pathologic feature of hyperuricemia that is highly prevalent and that contributes to kidney tubular interstitial fibrosis. Rho-kinase is closely related to mitochondrial-induced oxidative stress. Herein, we designed a study to explore the expression and role of Rho-kinase in hyperuricemia nephropathy. The secondary objective was to investigate whether the Rho-kinase signaling pathway regulates hyperuricemic tubular oxidative injury and apoptosis via the mitochondrial pathway in addition to the mechanisms that are involved.
Materials and methods
HK-2 cells were divided into the following five groups: normal; uric acid (UA); UA+Fasudil; UA+ROCK1 si-RNA; and UA+sc-siRNA. Rho-kinase activity, mitochondrial oxidative injury, and apoptosis-related protein levels were measured in each group. A t-test was used to analyze the difference between groups.
Results
Myosin phosphatase target subunit 1 (MYPT1) overexpression was shown in HK-2 cells, which was caused by UA. High concentrations of UA also up-regulated Rho-kinase expression and mitochondrial and apoptosis-related protein expression, while treatment with fasudil and ROCK1 si-RNA significantly attenuated these responses.
Conclusion
The Rho-kinase signaling pathway participates in tubular mitochondrial oxidative injury and apoptosis via regulating mitochondrial dyneins/biogenic genes in UA nephropathy, which suggests that the mitochondrial pathway might be a potential therapeutic target for hyperuricemia nephropathy.</abstract><cop>London, England</cop><pub>SAGE Publications</pub><pmid>34167354</pmid><doi>10.1177/03000605211021752</doi><orcidid>https://orcid.org/0000-0002-7546-6388</orcidid><oa>free_for_read</oa></addata></record> |
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| subjects | Apoptosis Cell Line Humans Kidney Diseases Kinases Mitochondria - pathology Oxidative Stress Pre-Clinical Research Report rho-Associated Kinases - genetics Signal Transduction Uric Acid |
| title | The Rho kinase signaling pathway participates in tubular mitochondrial oxidative injury and apoptosis in uric acid nephropathy |
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