Liver gene regulation of hemostasis-related factors is altered by experimental snake envenomation in mice
Few studies have addressed gene expression of hemostasis-related factors during acute thrombo-hemorrhagic diseases. Bites by the lanced-headed viper Bothrops jaracaca induce rapid hemostatic disturbances in victims, leading to systemic bleedings, thrombocytopenia and consumption coagulopathy. Althou...
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| description | Few studies have addressed gene expression of hemostasis-related factors during acute thrombo-hemorrhagic diseases. Bites by the lanced-headed viper Bothrops jaracaca induce rapid hemostatic disturbances in victims, leading to systemic bleedings, thrombocytopenia and consumption coagulopathy. Although circulating levels of coagulation factors recover rapidly after administration of specific antivenom therapy, it is unclear if B. jararaca venom (BjV) upregulates the mRNA synthesis of hepatic hemostasis-related factors, or if the recovery occurs under basal conditions after the neutralization of venom components by antivenom. Thus, we aimed to investigate if BjV regulates gene expression of important hemostasis-related factors synthetized by the liver. On that account, Swiss mice were injected with saline or BjV (1.6 mg/kg b.w, s.c.), and after 3, 6 and 24 h blood samples and liver fragments were collected to analyze mRNA expression by real-time qPCR. Increased gene expression of fibrinogen chains, haptoglobin and STAT3 was observed during envenomation, particularly at 3 and 6 h. At 24h, mRNA levels of F10 were raised, while those of Serpinc1, Proc and Adamts13 were diminished. Surprisingly, F3 mRNA levels were steadily decreased at 3 h. Gene expression of Thpo, F7, F5 Tfpi, Mug1 was unaltered. mRNA levels of Vwf, P4hb, F8, F2, Plg, and Serpinf2 were minimally altered, but showed important associations with Nfkb1 gene expression. In conclusion, snakebite envenomation upregulates hepatic mRNA synthesis particularly of fibrinogen chains, and acute-phase markers. This response explains the fast recovery of fibrinogen levels after antivenom administration to patients bitten by B. jararaca snakes. |
| doi_str_mv | 10.1371/journal.pntd.0008379 |
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Bites by the lanced-headed viper Bothrops jaracaca induce rapid hemostatic disturbances in victims, leading to systemic bleedings, thrombocytopenia and consumption coagulopathy. Although circulating levels of coagulation factors recover rapidly after administration of specific antivenom therapy, it is unclear if B. jararaca venom (BjV) upregulates the mRNA synthesis of hepatic hemostasis-related factors, or if the recovery occurs under basal conditions after the neutralization of venom components by antivenom. Thus, we aimed to investigate if BjV regulates gene expression of important hemostasis-related factors synthetized by the liver. On that account, Swiss mice were injected with saline or BjV (1.6 mg/kg b.w, s.c.), and after 3, 6 and 24 h blood samples and liver fragments were collected to analyze mRNA expression by real-time qPCR. Increased gene expression of fibrinogen chains, haptoglobin and STAT3 was observed during envenomation, particularly at 3 and 6 h. At 24h, mRNA levels of F10 were raised, while those of Serpinc1, Proc and Adamts13 were diminished. Surprisingly, F3 mRNA levels were steadily decreased at 3 h. Gene expression of Thpo, F7, F5 Tfpi, Mug1 was unaltered. mRNA levels of Vwf, P4hb, F8, F2, Plg, and Serpinf2 were minimally altered, but showed important associations with Nfkb1 gene expression. In conclusion, snakebite envenomation upregulates hepatic mRNA synthesis particularly of fibrinogen chains, and acute-phase markers. This response explains the fast recovery of fibrinogen levels after antivenom administration to patients bitten by B. jararaca snakes.</description><identifier>ISSN: 1935-2735</identifier><identifier>ISSN: 1935-2727</identifier><identifier>EISSN: 1935-2735</identifier><identifier>DOI: 10.1371/journal.pntd.0008379</identifier><identifier>PMID: 32479494</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Animals ; Antivenins ; Antivenins - therapeutic use ; Antivenom ; Biology and Life Sciences ; Bites ; Bites (Injuries) ; Bleeding ; Blood ; Blood Coagulation Disorders ; Blood coagulation factors ; Blood platelets ; Blood Proteins - genetics ; Bothrops - metabolism ; Bothrops jararaca ; Chains ; Coagulation ; Complications and side effects ; Disease Models, Animal ; Drug dosages ; Fibrinogen ; Fibrinogen - chemistry ; Fibrinogen - genetics ; Fibrinogen - metabolism ; Gene expression ; Gene Expression Regulation ; Gene regulation ; Genetic aspects ; Haptoglobin ; Haptoglobins - metabolism ; Health aspects ; Hemorrhage ; Hemostasis ; Hemostasis - genetics ; Hemostatics ; Laboratories ; Levels ; Liver ; Liver - metabolism ; Male ; Medicine and Health Sciences ; Mice ; Neutralization ; Pathophysiology ; Patient outcomes ; Plasma ; Proteins ; Recovery ; RNA, Messenger - metabolism ; Snake bites ; Snake Bites - blood ; Snake Bites - metabolism ; Snakes ; Stat3 protein ; STAT3 Transcription Factor - metabolism ; Synthesis ; Therapy ; Thrombocytopenia ; Time Factors ; Transcription ; Transcription Factors - genetics ; Tropical diseases ; Venom</subject><ispartof>PLoS neglected tropical diseases, 2020-06, Vol.14 (6), p.e0008379</ispartof><rights>COPYRIGHT 2020 Public Library of Science</rights><rights>2020 Sachetto 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>2020 Sachetto et al 2020 Sachetto et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c624t-83db218f004c5c489ad090cb7311e4386554db52b0e99b876e1f0eaf26f9da073</citedby><cites>FETCH-LOGICAL-c624t-83db218f004c5c489ad090cb7311e4386554db52b0e99b876e1f0eaf26f9da073</cites><orcidid>0000-0001-6228-2988 ; 0000-0001-6364-3757</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/PMC7289449/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7289449/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,864,885,2102,2928,23866,27924,27925,53791,53793,79600,79601</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/32479494$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Lacerda, Marcus VG</contributor><creatorcontrib>Sachetto, Ana Teresa Azevedo</creatorcontrib><creatorcontrib>Jensen, José Ricardo</creatorcontrib><creatorcontrib>Santoro, Marcelo Larami</creatorcontrib><title>Liver gene regulation of hemostasis-related factors is altered by experimental snake envenomation in mice</title><title>PLoS neglected tropical diseases</title><addtitle>PLoS Negl Trop Dis</addtitle><description>Few studies have addressed gene expression of hemostasis-related factors during acute thrombo-hemorrhagic diseases. Bites by the lanced-headed viper Bothrops jaracaca induce rapid hemostatic disturbances in victims, leading to systemic bleedings, thrombocytopenia and consumption coagulopathy. Although circulating levels of coagulation factors recover rapidly after administration of specific antivenom therapy, it is unclear if B. jararaca venom (BjV) upregulates the mRNA synthesis of hepatic hemostasis-related factors, or if the recovery occurs under basal conditions after the neutralization of venom components by antivenom. Thus, we aimed to investigate if BjV regulates gene expression of important hemostasis-related factors synthetized by the liver. On that account, Swiss mice were injected with saline or BjV (1.6 mg/kg b.w, s.c.), and after 3, 6 and 24 h blood samples and liver fragments were collected to analyze mRNA expression by real-time qPCR. Increased gene expression of fibrinogen chains, haptoglobin and STAT3 was observed during envenomation, particularly at 3 and 6 h. At 24h, mRNA levels of F10 were raised, while those of Serpinc1, Proc and Adamts13 were diminished. Surprisingly, F3 mRNA levels were steadily decreased at 3 h. Gene expression of Thpo, F7, F5 Tfpi, Mug1 was unaltered. mRNA levels of Vwf, P4hb, F8, F2, Plg, and Serpinf2 were minimally altered, but showed important associations with Nfkb1 gene expression. In conclusion, snakebite envenomation upregulates hepatic mRNA synthesis particularly of fibrinogen chains, and acute-phase markers. This response explains the fast recovery of fibrinogen levels after antivenom administration to patients bitten by B. jararaca snakes.</description><subject>Animals</subject><subject>Antivenins</subject><subject>Antivenins - therapeutic use</subject><subject>Antivenom</subject><subject>Biology and Life Sciences</subject><subject>Bites</subject><subject>Bites (Injuries)</subject><subject>Bleeding</subject><subject>Blood</subject><subject>Blood Coagulation Disorders</subject><subject>Blood coagulation factors</subject><subject>Blood platelets</subject><subject>Blood Proteins - genetics</subject><subject>Bothrops - metabolism</subject><subject>Bothrops jararaca</subject><subject>Chains</subject><subject>Coagulation</subject><subject>Complications and side effects</subject><subject>Disease Models, Animal</subject><subject>Drug dosages</subject><subject>Fibrinogen</subject><subject>Fibrinogen - chemistry</subject><subject>Fibrinogen - genetics</subject><subject>Fibrinogen - metabolism</subject><subject>Gene expression</subject><subject>Gene Expression Regulation</subject><subject>Gene regulation</subject><subject>Genetic aspects</subject><subject>Haptoglobin</subject><subject>Haptoglobins - metabolism</subject><subject>Health aspects</subject><subject>Hemorrhage</subject><subject>Hemostasis</subject><subject>Hemostasis - genetics</subject><subject>Hemostatics</subject><subject>Laboratories</subject><subject>Levels</subject><subject>Liver</subject><subject>Liver - metabolism</subject><subject>Male</subject><subject>Medicine and Health Sciences</subject><subject>Mice</subject><subject>Neutralization</subject><subject>Pathophysiology</subject><subject>Patient outcomes</subject><subject>Plasma</subject><subject>Proteins</subject><subject>Recovery</subject><subject>RNA, Messenger - metabolism</subject><subject>Snake bites</subject><subject>Snake Bites - blood</subject><subject>Snake Bites - metabolism</subject><subject>Snakes</subject><subject>Stat3 protein</subject><subject>STAT3 Transcription Factor - metabolism</subject><subject>Synthesis</subject><subject>Therapy</subject><subject>Thrombocytopenia</subject><subject>Time Factors</subject><subject>Transcription</subject><subject>Transcription Factors - genetics</subject><subject>Tropical diseases</subject><subject>Venom</subject><issn>1935-2735</issn><issn>1935-2727</issn><issn>1935-2735</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><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>eNp1Ul2LEzEUHURx19V_IBoQfGvN50zyIiyLHwsFX_Q55ONOmzqT1GS6uP_e1M4uLSh5SDg59-Tk3tM0rwleEtaRD9u0z9EMy12c_BJjLFmnnjSXRDGxoB0TT0_OF82LUrYYCyUked5cMMo7xRW_bMIq3EFGa4iAMqz3g5lCiij1aANjKpMpoSwyVBg86o2bUi4oFGSGCXKF7D2C3zvIYYQ4mQGVaH4CgngHMY1HrRDRGBy8bJ71Zijwat6vmh-fP32_-bpYfftye3O9WriW8mkhmbeUyB5j7oTjUhmPFXa2Y4QAZ7IVgnsrqMWglJVdC6THYHra9sob3LGr5u1RdzekoucuFU055bztWCsr4_bI8Mls9a56N_leJxP0XyDltTZ5Cm4ALazHVngqvJXcAJe0NcZbcjAmpCNV6-P82t6O4F3tQjbDmej5TQwbvU53uqNSca6qwLtZIKdfeyjTfyzPrLWprkLsUxVzYyhOX7eMqrYT7UFr-Q9WXR7qBFKEPlT8rOD9ScEG6lQ3JQ37w9zKOZEfiS6nUjL0jz8kWB_i-OBaH-Ko5zjWsjen3Xksesgf-wOAVN48</recordid><startdate>202006</startdate><enddate>202006</enddate><creator>Sachetto, Ana Teresa Azevedo</creator><creator>Jensen, José Ricardo</creator><creator>Santoro, Marcelo Larami</creator><general>Public Library of Science</general><general>Public Library of Science (PLoS)</general><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>7QL</scope><scope>7SS</scope><scope>7T2</scope><scope>7T7</scope><scope>7U9</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8C1</scope><scope>8FD</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BENPR</scope><scope>C1K</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>F1W</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>H94</scope><scope>H95</scope><scope>H97</scope><scope>K9.</scope><scope>L.G</scope><scope>M0S</scope><scope>M1P</scope><scope>M7N</scope><scope>P64</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>5PM</scope><scope>DOA</scope><orcidid>https://orcid.org/0000-0001-6228-2988</orcidid><orcidid>https://orcid.org/0000-0001-6364-3757</orcidid></search><sort><creationdate>202006</creationdate><title>Liver gene regulation of hemostasis-related factors is altered by experimental snake envenomation in mice</title><author>Sachetto, Ana Teresa Azevedo ; Jensen, José Ricardo ; Santoro, Marcelo Larami</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c624t-83db218f004c5c489ad090cb7311e4386554db52b0e99b876e1f0eaf26f9da073</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>Animals</topic><topic>Antivenins</topic><topic>Antivenins - therapeutic use</topic><topic>Antivenom</topic><topic>Biology and Life Sciences</topic><topic>Bites</topic><topic>Bites (Injuries)</topic><topic>Bleeding</topic><topic>Blood</topic><topic>Blood Coagulation Disorders</topic><topic>Blood coagulation factors</topic><topic>Blood platelets</topic><topic>Blood Proteins - genetics</topic><topic>Bothrops - metabolism</topic><topic>Bothrops jararaca</topic><topic>Chains</topic><topic>Coagulation</topic><topic>Complications and side effects</topic><topic>Disease Models, Animal</topic><topic>Drug dosages</topic><topic>Fibrinogen</topic><topic>Fibrinogen - chemistry</topic><topic>Fibrinogen - genetics</topic><topic>Fibrinogen - metabolism</topic><topic>Gene expression</topic><topic>Gene Expression Regulation</topic><topic>Gene regulation</topic><topic>Genetic aspects</topic><topic>Haptoglobin</topic><topic>Haptoglobins - metabolism</topic><topic>Health aspects</topic><topic>Hemorrhage</topic><topic>Hemostasis</topic><topic>Hemostasis - genetics</topic><topic>Hemostatics</topic><topic>Laboratories</topic><topic>Levels</topic><topic>Liver</topic><topic>Liver - 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Bites by the lanced-headed viper Bothrops jaracaca induce rapid hemostatic disturbances in victims, leading to systemic bleedings, thrombocytopenia and consumption coagulopathy. Although circulating levels of coagulation factors recover rapidly after administration of specific antivenom therapy, it is unclear if B. jararaca venom (BjV) upregulates the mRNA synthesis of hepatic hemostasis-related factors, or if the recovery occurs under basal conditions after the neutralization of venom components by antivenom. Thus, we aimed to investigate if BjV regulates gene expression of important hemostasis-related factors synthetized by the liver. On that account, Swiss mice were injected with saline or BjV (1.6 mg/kg b.w, s.c.), and after 3, 6 and 24 h blood samples and liver fragments were collected to analyze mRNA expression by real-time qPCR. Increased gene expression of fibrinogen chains, haptoglobin and STAT3 was observed during envenomation, particularly at 3 and 6 h. At 24h, mRNA levels of F10 were raised, while those of Serpinc1, Proc and Adamts13 were diminished. Surprisingly, F3 mRNA levels were steadily decreased at 3 h. Gene expression of Thpo, F7, F5 Tfpi, Mug1 was unaltered. mRNA levels of Vwf, P4hb, F8, F2, Plg, and Serpinf2 were minimally altered, but showed important associations with Nfkb1 gene expression. In conclusion, snakebite envenomation upregulates hepatic mRNA synthesis particularly of fibrinogen chains, and acute-phase markers. This response explains the fast recovery of fibrinogen levels after antivenom administration to patients bitten by B. jararaca snakes.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>32479494</pmid><doi>10.1371/journal.pntd.0008379</doi><orcidid>https://orcid.org/0000-0001-6228-2988</orcidid><orcidid>https://orcid.org/0000-0001-6364-3757</orcidid><oa>free_for_read</oa></addata></record> |
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| ispartof | PLoS neglected tropical diseases, 2020-06, Vol.14 (6), p.e0008379 |
| issn | 1935-2735 1935-2727 1935-2735 |
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| source | MEDLINE; DOAJ Directory of Open Access Journals; PubMed Central Open Access; Public Library of Science (PLoS) Journals Open Access; EZB-FREE-00999 freely available EZB journals; PubMed Central |
| subjects | Animals Antivenins Antivenins - therapeutic use Antivenom Biology and Life Sciences Bites Bites (Injuries) Bleeding Blood Blood Coagulation Disorders Blood coagulation factors Blood platelets Blood Proteins - genetics Bothrops - metabolism Bothrops jararaca Chains Coagulation Complications and side effects Disease Models, Animal Drug dosages Fibrinogen Fibrinogen - chemistry Fibrinogen - genetics Fibrinogen - metabolism Gene expression Gene Expression Regulation Gene regulation Genetic aspects Haptoglobin Haptoglobins - metabolism Health aspects Hemorrhage Hemostasis Hemostasis - genetics Hemostatics Laboratories Levels Liver Liver - metabolism Male Medicine and Health Sciences Mice Neutralization Pathophysiology Patient outcomes Plasma Proteins Recovery RNA, Messenger - metabolism Snake bites Snake Bites - blood Snake Bites - metabolism Snakes Stat3 protein STAT3 Transcription Factor - metabolism Synthesis Therapy Thrombocytopenia Time Factors Transcription Transcription Factors - genetics Tropical diseases Venom |
| title | Liver gene regulation of hemostasis-related factors is altered by experimental snake envenomation in mice |
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