Regulation of SARS CoV-2 host factors in the kidney and heart in rats with 5/6 nephrectomy—effects of salt, ARB, DPP4 inhibitor and SGLT2 blocker
Abstract Background Host factors such as angiotensin-converting enzyme 2 (ACE2) and the transmembrane protease, serine-subtype-2 (TMPRSS2) are important factors for SARS-CoV-2 infection. Clinical and pre-clinical studies demonstrated that RAAS-blocking agents can be safely used during a SARS-CoV-2 i...
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| Format: | Article |
| Language: | English |
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BMC
2022-03-01
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| Series: | BMC Nephrology |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12882-022-02747-1 |
| _version_ | 1818776620474826752 |
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| author | Yingquan Xiong Denis Delic Shufei Zeng Xin Chen Chang Chu Ahmed A. Hasan Bernhard K. Krämer Thomas Klein Lianghong Yin Berthold Hocher |
| author_facet | Yingquan Xiong Denis Delic Shufei Zeng Xin Chen Chang Chu Ahmed A. Hasan Bernhard K. Krämer Thomas Klein Lianghong Yin Berthold Hocher |
| author_sort | Yingquan Xiong |
| collection | DOAJ |
| description | Abstract Background Host factors such as angiotensin-converting enzyme 2 (ACE2) and the transmembrane protease, serine-subtype-2 (TMPRSS2) are important factors for SARS-CoV-2 infection. Clinical and pre-clinical studies demonstrated that RAAS-blocking agents can be safely used during a SARS-CoV-2 infection but it is unknown if DPP-4 inhibitors or SGLT2-blockers may promote COVID-19 by increasing the host viral entry enzymes ACE2 and TMPRSS2. Methods We investigated telmisartan, linagliptin and empagliflozin induced effects on renal and cardiac expression of ACE2, TMPRSS2 and key enzymes involved in RAAS (REN, AGTR2, AGT) under high-salt conditions in a non-diabetic experimental 5/6 nephrectomy (5/6 Nx) model. In the present study, the gene expression of Ace2, Tmprss2, Ren, Agtr2 and Agt was assessed with qRT-PCR and the protein expression of ACE2 and TMPRSS2 with immunohistochemistry in the following experimental groups: Sham + normal diet (ND) + placebo (PBO); 5/6Nx + ND + PBO; 5/6Nx + high salt-diet (HSD) + PBO; 5/6Nx + HSD + telmisartan; 5/6Nx + HSD + linagliptin; 5/6Nx + HSD + empagliflozin. Results In the kidney, the expression of Ace2 was not altered on mRNA level under disease and treatment conditions. The renal TMPRSS2 levels (mRNA and protein) were not affected, whereas the cardiac level was significantly increased in 5/6Nx rats. Intriguingly, the elevated TMPRSS2 protein expression in the heart was significantly normalized after treatment with telmisartan, linagliptin and empagliflozin. Conclusions Our study indicated that there is no upregulation regarding host factors potentially promoting SARS-CoV-2 virus entry into host cells when the SGLT2-blocker empagliflozin, telmisartan and the DPP4-inhibitor blocker linagliptin are used. The results obtained in a preclinical, experimental non-diabetic kidney failure model need confirmation in ongoing interventional clinical trials. |
| first_indexed | 2024-12-18T11:15:50Z |
| format | Article |
| id | doaj.art-d0d3f6c070c84a6a9554fc0945f7e423 |
| institution | Directory Open Access Journal |
| issn | 1471-2369 |
| language | English |
| last_indexed | 2024-12-18T11:15:50Z |
| publishDate | 2022-03-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Nephrology |
| spelling | doaj.art-d0d3f6c070c84a6a9554fc0945f7e4232022-12-21T21:09:56ZengBMCBMC Nephrology1471-23692022-03-0123111010.1186/s12882-022-02747-1Regulation of SARS CoV-2 host factors in the kidney and heart in rats with 5/6 nephrectomy—effects of salt, ARB, DPP4 inhibitor and SGLT2 blockerYingquan Xiong0Denis Delic1Shufei Zeng2Xin Chen3Chang Chu4Ahmed A. Hasan5Bernhard K. Krämer6Thomas Klein7Lianghong Yin8Berthold Hocher9Fifth Department of Medicine (Nephrology/Endocrinology/Rheumatology), University Medical Centre Mannheim, University of HeidelbergFifth Department of Medicine (Nephrology/Endocrinology/Rheumatology), University Medical Centre Mannheim, University of HeidelbergDepartment of Nephrology, Charité - Universitätsmedizin BerlinDepartment of Nephrology, Charité - Universitätsmedizin BerlinDepartment of Nephrology, Charité - Universitätsmedizin BerlinFifth Department of Medicine (Nephrology/Endocrinology/Rheumatology), University Medical Centre Mannheim, University of HeidelbergFifth Department of Medicine (Nephrology/Endocrinology/Rheumatology), University Medical Centre Mannheim, University of HeidelbergBoehringer Ingelheim Pharma GmbH & Co. KGDepartment of Nephrology, the First Affiliated Hospital of Jinan UniversityFifth Department of Medicine (Nephrology/Endocrinology/Rheumatology), University Medical Centre Mannheim, University of HeidelbergAbstract Background Host factors such as angiotensin-converting enzyme 2 (ACE2) and the transmembrane protease, serine-subtype-2 (TMPRSS2) are important factors for SARS-CoV-2 infection. Clinical and pre-clinical studies demonstrated that RAAS-blocking agents can be safely used during a SARS-CoV-2 infection but it is unknown if DPP-4 inhibitors or SGLT2-blockers may promote COVID-19 by increasing the host viral entry enzymes ACE2 and TMPRSS2. Methods We investigated telmisartan, linagliptin and empagliflozin induced effects on renal and cardiac expression of ACE2, TMPRSS2 and key enzymes involved in RAAS (REN, AGTR2, AGT) under high-salt conditions in a non-diabetic experimental 5/6 nephrectomy (5/6 Nx) model. In the present study, the gene expression of Ace2, Tmprss2, Ren, Agtr2 and Agt was assessed with qRT-PCR and the protein expression of ACE2 and TMPRSS2 with immunohistochemistry in the following experimental groups: Sham + normal diet (ND) + placebo (PBO); 5/6Nx + ND + PBO; 5/6Nx + high salt-diet (HSD) + PBO; 5/6Nx + HSD + telmisartan; 5/6Nx + HSD + linagliptin; 5/6Nx + HSD + empagliflozin. Results In the kidney, the expression of Ace2 was not altered on mRNA level under disease and treatment conditions. The renal TMPRSS2 levels (mRNA and protein) were not affected, whereas the cardiac level was significantly increased in 5/6Nx rats. Intriguingly, the elevated TMPRSS2 protein expression in the heart was significantly normalized after treatment with telmisartan, linagliptin and empagliflozin. Conclusions Our study indicated that there is no upregulation regarding host factors potentially promoting SARS-CoV-2 virus entry into host cells when the SGLT2-blocker empagliflozin, telmisartan and the DPP4-inhibitor blocker linagliptin are used. The results obtained in a preclinical, experimental non-diabetic kidney failure model need confirmation in ongoing interventional clinical trials.https://doi.org/10.1186/s12882-022-02747-1SARS CoV-2 host factors5/6 nephrectomyHigh-salt dietARBDPP4 inhibitorSGLT2 blocker |
| spellingShingle | Yingquan Xiong Denis Delic Shufei Zeng Xin Chen Chang Chu Ahmed A. Hasan Bernhard K. Krämer Thomas Klein Lianghong Yin Berthold Hocher Regulation of SARS CoV-2 host factors in the kidney and heart in rats with 5/6 nephrectomy—effects of salt, ARB, DPP4 inhibitor and SGLT2 blocker BMC Nephrology SARS CoV-2 host factors 5/6 nephrectomy High-salt diet ARB DPP4 inhibitor SGLT2 blocker |
| title | Regulation of SARS CoV-2 host factors in the kidney and heart in rats with 5/6 nephrectomy—effects of salt, ARB, DPP4 inhibitor and SGLT2 blocker |
| title_full | Regulation of SARS CoV-2 host factors in the kidney and heart in rats with 5/6 nephrectomy—effects of salt, ARB, DPP4 inhibitor and SGLT2 blocker |
| title_fullStr | Regulation of SARS CoV-2 host factors in the kidney and heart in rats with 5/6 nephrectomy—effects of salt, ARB, DPP4 inhibitor and SGLT2 blocker |
| title_full_unstemmed | Regulation of SARS CoV-2 host factors in the kidney and heart in rats with 5/6 nephrectomy—effects of salt, ARB, DPP4 inhibitor and SGLT2 blocker |
| title_short | Regulation of SARS CoV-2 host factors in the kidney and heart in rats with 5/6 nephrectomy—effects of salt, ARB, DPP4 inhibitor and SGLT2 blocker |
| title_sort | regulation of sars cov 2 host factors in the kidney and heart in rats with 5 6 nephrectomy effects of salt arb dpp4 inhibitor and sglt2 blocker |
| topic | SARS CoV-2 host factors 5/6 nephrectomy High-salt diet ARB DPP4 inhibitor SGLT2 blocker |
| url | https://doi.org/10.1186/s12882-022-02747-1 |
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