Regulation of Paneth cell-specific genes in COVID-19 patients and SARS-CoV-2-infected mice by quantification of mRNA from exfoliated cells in stool samples
Abstract The Paneth cell, a secretory cell of the small intestine, expresses numerous host defense proteins, and is hypothesized to play an important role in host defense against infection. However, studying gene expression in this cell requires invasive procedures. To test the hypothesis that we co...
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Nature Portfolio
2024-12-01
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| Online Access: | https://doi.org/10.1038/s41598-024-82098-z |
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| author | Gill Diamond Erika L. Figgins Denny Gao Tanya O. Robinson Kenneth Wilson Jon D. Gabbard Charles D. Anderson Lalit Batra Chithra Sreenivasan Jian Zheng Uyen Do Braden Mulcahy Lisa K. Ryan Nathaniel McLaughlin Anna H. Owings Neha Dhaliwal Haley B. Williams T. Grant Wichman Michelle Galeas-Pena Sarah C. Glover |
| author_facet | Gill Diamond Erika L. Figgins Denny Gao Tanya O. Robinson Kenneth Wilson Jon D. Gabbard Charles D. Anderson Lalit Batra Chithra Sreenivasan Jian Zheng Uyen Do Braden Mulcahy Lisa K. Ryan Nathaniel McLaughlin Anna H. Owings Neha Dhaliwal Haley B. Williams T. Grant Wichman Michelle Galeas-Pena Sarah C. Glover |
| author_sort | Gill Diamond |
| collection | DOAJ |
| description | Abstract The Paneth cell, a secretory cell of the small intestine, expresses numerous host defense proteins, and is hypothesized to play an important role in host defense against infection. However, studying gene expression in this cell requires invasive procedures. To test the hypothesis that we could observe Paneth cell-specific gene regulation from exfoliated cells in infectious conditions, we obtained stool samples from patients with COVID-19 and uninfected controls. Total mRNA was isolated, and Paneth cell-specific and non-specific gene expression was quantified by RT-PCR. Results revealed a significant decrease in mRNA levels from Paneth cell-specific genes, including DEFA5, DEFA6, PLA2G2A, PRSS2 and ITLN2 in SARS-CoV-2 positive patients compared with controls. Other gut markers, not specific to Paneth cells were unchanged. To validate this experimentally, we infected mice with SARS-CoV-2 and collected fecal pellets over the course of 7 days. We observed a similar time-dependent reduction in Paneth cell-specific transcripts, which correlates with histological changes in the gut. This is the first demonstration of quantification of Paneth cell-specific transcripts without invasive sampling. It also shows the coordinate regulation of these genes as a response to infection with SARS-CoV-2, possibly through viral pathogenesis, to increase infectivity in the gut. |
| format | Article |
| id | doaj-art-dc2191ac3ac6400284a462f3c8e1efde |
| institution | Kabale University |
| issn | 2045-2322 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj-art-dc2191ac3ac6400284a462f3c8e1efde2025-01-05T12:26:38ZengNature PortfolioScientific Reports2045-23222024-12-011411910.1038/s41598-024-82098-zRegulation of Paneth cell-specific genes in COVID-19 patients and SARS-CoV-2-infected mice by quantification of mRNA from exfoliated cells in stool samplesGill Diamond0Erika L. Figgins1Denny Gao2Tanya O. Robinson3Kenneth Wilson4Jon D. Gabbard5Charles D. Anderson6Lalit Batra7Chithra Sreenivasan8Jian Zheng9Uyen Do10Braden Mulcahy11Lisa K. Ryan12Nathaniel McLaughlin13Anna H. Owings14Neha Dhaliwal15Haley B. Williams16T. Grant Wichman17Michelle Galeas-Pena18Sarah C. Glover19Department of Oral Immunology and Infectious Diseases, University of Louisville School of DentistryDepartment of Oral Immunology and Infectious Diseases, University of Louisville School of DentistryDepartment of Oral Immunology and Infectious Diseases, University of Louisville School of DentistryDivision of Gastroenterology, University of Mississippi Medical CenterDivision of Gastroenterology, University of Mississippi Medical CenterCenter for Predictive Medicine for Biodefence and Emerging Infectious Diseases, University of LouisvilleCenter for Predictive Medicine for Biodefence and Emerging Infectious Diseases, University of LouisvilleCenter for Predictive Medicine for Biodefence and Emerging Infectious Diseases, University of LouisvilleCenter for Predictive Medicine for Biodefence and Emerging Infectious Diseases, University of LouisvilleCenter for Predictive Medicine for Biodefence and Emerging Infectious Diseases, University of LouisvilleDepartment of Oral Immunology and Infectious Diseases, University of Louisville School of DentistryDepartment of Oral Immunology and Infectious Diseases, University of Louisville School of DentistryDepartment of Oral Immunology and Infectious Diseases, University of Louisville School of DentistryDepartment of Pathology and Laboratory Medicine, Thibodaux Regional Health SystemDivision of Gastroenterology, University of Mississippi Medical CenterDivision of Gastroenterology, University of Mississippi Medical CenterDivision of Gastroenterology, University of Mississippi Medical CenterDivision of Gastroenterology, University of Mississippi Medical CenterDivision of Gastroenterology and Hepatology, Department of Medicine, Tulane University School of MedicineDivision of Gastroenterology, University of Mississippi Medical CenterAbstract The Paneth cell, a secretory cell of the small intestine, expresses numerous host defense proteins, and is hypothesized to play an important role in host defense against infection. However, studying gene expression in this cell requires invasive procedures. To test the hypothesis that we could observe Paneth cell-specific gene regulation from exfoliated cells in infectious conditions, we obtained stool samples from patients with COVID-19 and uninfected controls. Total mRNA was isolated, and Paneth cell-specific and non-specific gene expression was quantified by RT-PCR. Results revealed a significant decrease in mRNA levels from Paneth cell-specific genes, including DEFA5, DEFA6, PLA2G2A, PRSS2 and ITLN2 in SARS-CoV-2 positive patients compared with controls. Other gut markers, not specific to Paneth cells were unchanged. To validate this experimentally, we infected mice with SARS-CoV-2 and collected fecal pellets over the course of 7 days. We observed a similar time-dependent reduction in Paneth cell-specific transcripts, which correlates with histological changes in the gut. This is the first demonstration of quantification of Paneth cell-specific transcripts without invasive sampling. It also shows the coordinate regulation of these genes as a response to infection with SARS-CoV-2, possibly through viral pathogenesis, to increase infectivity in the gut.https://doi.org/10.1038/s41598-024-82098-zSmall intestineBiomarkerSARS-CoV-2Defensin |
| spellingShingle | Gill Diamond Erika L. Figgins Denny Gao Tanya O. Robinson Kenneth Wilson Jon D. Gabbard Charles D. Anderson Lalit Batra Chithra Sreenivasan Jian Zheng Uyen Do Braden Mulcahy Lisa K. Ryan Nathaniel McLaughlin Anna H. Owings Neha Dhaliwal Haley B. Williams T. Grant Wichman Michelle Galeas-Pena Sarah C. Glover Regulation of Paneth cell-specific genes in COVID-19 patients and SARS-CoV-2-infected mice by quantification of mRNA from exfoliated cells in stool samples Scientific Reports Small intestine Biomarker SARS-CoV-2 Defensin |
| title | Regulation of Paneth cell-specific genes in COVID-19 patients and SARS-CoV-2-infected mice by quantification of mRNA from exfoliated cells in stool samples |
| title_full | Regulation of Paneth cell-specific genes in COVID-19 patients and SARS-CoV-2-infected mice by quantification of mRNA from exfoliated cells in stool samples |
| title_fullStr | Regulation of Paneth cell-specific genes in COVID-19 patients and SARS-CoV-2-infected mice by quantification of mRNA from exfoliated cells in stool samples |
| title_full_unstemmed | Regulation of Paneth cell-specific genes in COVID-19 patients and SARS-CoV-2-infected mice by quantification of mRNA from exfoliated cells in stool samples |
| title_short | Regulation of Paneth cell-specific genes in COVID-19 patients and SARS-CoV-2-infected mice by quantification of mRNA from exfoliated cells in stool samples |
| title_sort | regulation of paneth cell specific genes in covid 19 patients and sars cov 2 infected mice by quantification of mrna from exfoliated cells in stool samples |
| topic | Small intestine Biomarker SARS-CoV-2 Defensin |
| url | https://doi.org/10.1038/s41598-024-82098-z |
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