Single-cell RNA sequencing reveals cellular dynamics and therapeutic effects of astragaloside IV in slow transit constipation
The cellular characteristics of intestinal cells involved in the therapeutic effects of astragaloside IV (AS-IV) for treating slow transit constipation (STC) remain unclear. This study aimed to determine the dynamics of colon tissue cells in the STC model and investigate the effects of AS-IV treatm...
| Main Authors: | , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Association of Basic Medical Sciences of Federation of Bosnia and Herzegovina
2024-01-01
|
| Series: | Biomolecules & Biomedicine |
| Subjects: | |
| Online Access: | https://www.bjbms.org/ojs/index.php/bjbms/article/view/10187 |
| _version_ | 1797261397519761408 |
|---|---|
| author | Huaxian Chen Xingyang Wan Qiulan He Guozhong Xiao Yihui Zheng Minyi Luo Chaoxin Yang Donglin Ren Li Lu Hui Peng Hongcheng Lin |
| author_facet | Huaxian Chen Xingyang Wan Qiulan He Guozhong Xiao Yihui Zheng Minyi Luo Chaoxin Yang Donglin Ren Li Lu Hui Peng Hongcheng Lin |
| author_sort | Huaxian Chen |
| collection | DOAJ |
| description |
The cellular characteristics of intestinal cells involved in the therapeutic effects of astragaloside IV (AS-IV) for treating slow transit constipation (STC) remain unclear. This study aimed to determine the dynamics of colon tissue cells in the STC model and investigate the effects of AS-IV treatment by single-cell RNA sequencing (scRNA-seq). STC mouse models were developed using loperamide, with subsequent treatment using AS-IV. Colon tissues and feces were collected for scRNA-seq and targeted short-chain fatty acid quantification. We integrated scRNA-seq data with network pharmacology to analyze the effect of AS-IV on constipation. AS-IV showed improvement in defecation for STC mice induced by loperamide. Notably, in STC mice, epithelial cells, T cells, B cells, and fibroblasts demonstrated alterations in cell proportions and aberrant functions, which AS-IV partially rectified. AS-IV has the potential to modulate the metabolic pathway of epithelial cells through its interaction with peroxisome proliferator-activated receptor gamma (PPARγ). AS-IV reinstated fecal butyrate levels and improved energy metabolism in epithelial cells. The proportion of naïve CD4+T cells is elevated in STC, and the differentiation of these cells into regulatory T cells (Treg) is regulated by B cells and fibroblasts through the interaction of ligand-receptor pairs. AS-IV treatment can partially alleviate this trend. The status of fibroblasts in STC undergoes alterations, and the FB_C4_Adamdec1 subset, associated with angiogenesis and the Wingless-related integration (Wnt) pathway, emerges. Our comprehensive analysis identifies perturbations of epithelial cells and tissue microenvironment cells in STC and elucidates mechanisms underlying the therapeutic efficacy of AS-IV.
|
| first_indexed | 2024-04-24T23:40:34Z |
| format | Article |
| id | doaj.art-d19d8d84154f460e847126dc60e2dbb4 |
| institution | Directory Open Access Journal |
| issn | 2831-0896 2831-090X |
| language | English |
| last_indexed | 2024-04-24T23:40:34Z |
| publishDate | 2024-01-01 |
| publisher | Association of Basic Medical Sciences of Federation of Bosnia and Herzegovina |
| record_format | Article |
| series | Biomolecules & Biomedicine |
| spelling | doaj.art-d19d8d84154f460e847126dc60e2dbb42024-03-15T13:20:52ZengAssociation of Basic Medical Sciences of Federation of Bosnia and HerzegovinaBiomolecules & Biomedicine2831-08962831-090X2024-01-0110.17305/bb.2024.10187Single-cell RNA sequencing reveals cellular dynamics and therapeutic effects of astragaloside IV in slow transit constipationHuaxian Chen0Xingyang Wan1Qiulan He2https://orcid.org/0000-0001-7514-3928Guozhong Xiao3Yihui Zheng4https://orcid.org/0000-0001-7403-9512Minyi Luo5Chaoxin Yang6Donglin Ren7Li Lu8Hui Peng9Hongcheng Lin10https://orcid.org/0000-0001-8893-9300Department of General Surgery (Department of Coloproctology), The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China; Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China; Biomedical Innovation Center, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, ChinaDepartment of General Surgery (Department of Coloproctology), The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China; Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China; Biomedical Innovation Center, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, ChinaDepartment of Anaesthesiology, First Affiliated Hospital of Sun Yat-sen University, Guangzhou, ChinaDepartment of General Surgery (Department of Coloproctology), The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China; Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China; Biomedical Innovation Center, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, ChinaDepartment of General Surgery (Department of Coloproctology), The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China; Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China; Biomedical Innovation Center, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, ChinaDepartment of General Surgery (Department of Coloproctology), The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China; Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China; Biomedical Innovation Center, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, ChinaDepartment of General Surgery (Department of Coloproctology), The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China; Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China; Biomedical Innovation Center, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, ChinaDepartment of General Surgery (Department of Coloproctology), The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China; Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China; Biomedical Innovation Center, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, ChinaDepartment of General Surgery (Department of Coloproctology), The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China; Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China; Biomedical Innovation Center, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, ChinaDepartment of General Surgery (Department of Coloproctology), The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China; Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China; Biomedical Innovation Center, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, ChinaDepartment of General Surgery (Department of Coloproctology), The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China; Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China; Biomedical Innovation Center, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China The cellular characteristics of intestinal cells involved in the therapeutic effects of astragaloside IV (AS-IV) for treating slow transit constipation (STC) remain unclear. This study aimed to determine the dynamics of colon tissue cells in the STC model and investigate the effects of AS-IV treatment by single-cell RNA sequencing (scRNA-seq). STC mouse models were developed using loperamide, with subsequent treatment using AS-IV. Colon tissues and feces were collected for scRNA-seq and targeted short-chain fatty acid quantification. We integrated scRNA-seq data with network pharmacology to analyze the effect of AS-IV on constipation. AS-IV showed improvement in defecation for STC mice induced by loperamide. Notably, in STC mice, epithelial cells, T cells, B cells, and fibroblasts demonstrated alterations in cell proportions and aberrant functions, which AS-IV partially rectified. AS-IV has the potential to modulate the metabolic pathway of epithelial cells through its interaction with peroxisome proliferator-activated receptor gamma (PPARγ). AS-IV reinstated fecal butyrate levels and improved energy metabolism in epithelial cells. The proportion of naïve CD4+T cells is elevated in STC, and the differentiation of these cells into regulatory T cells (Treg) is regulated by B cells and fibroblasts through the interaction of ligand-receptor pairs. AS-IV treatment can partially alleviate this trend. The status of fibroblasts in STC undergoes alterations, and the FB_C4_Adamdec1 subset, associated with angiogenesis and the Wingless-related integration (Wnt) pathway, emerges. Our comprehensive analysis identifies perturbations of epithelial cells and tissue microenvironment cells in STC and elucidates mechanisms underlying the therapeutic efficacy of AS-IV. https://www.bjbms.org/ojs/index.php/bjbms/article/view/10187Slow transit constipation, astragaloside IV (AS-IV), single-cell RNA sequencing, cellular dynamic, intestinal cells |
| spellingShingle | Huaxian Chen Xingyang Wan Qiulan He Guozhong Xiao Yihui Zheng Minyi Luo Chaoxin Yang Donglin Ren Li Lu Hui Peng Hongcheng Lin Single-cell RNA sequencing reveals cellular dynamics and therapeutic effects of astragaloside IV in slow transit constipation Biomolecules & Biomedicine Slow transit constipation, astragaloside IV (AS-IV), single-cell RNA sequencing, cellular dynamic, intestinal cells |
| title | Single-cell RNA sequencing reveals cellular dynamics and therapeutic effects of astragaloside IV in slow transit constipation |
| title_full | Single-cell RNA sequencing reveals cellular dynamics and therapeutic effects of astragaloside IV in slow transit constipation |
| title_fullStr | Single-cell RNA sequencing reveals cellular dynamics and therapeutic effects of astragaloside IV in slow transit constipation |
| title_full_unstemmed | Single-cell RNA sequencing reveals cellular dynamics and therapeutic effects of astragaloside IV in slow transit constipation |
| title_short | Single-cell RNA sequencing reveals cellular dynamics and therapeutic effects of astragaloside IV in slow transit constipation |
| title_sort | single cell rna sequencing reveals cellular dynamics and therapeutic effects of astragaloside iv in slow transit constipation |
| topic | Slow transit constipation, astragaloside IV (AS-IV), single-cell RNA sequencing, cellular dynamic, intestinal cells |
| url | https://www.bjbms.org/ojs/index.php/bjbms/article/view/10187 |
| work_keys_str_mv | AT huaxianchen singlecellrnasequencingrevealscellulardynamicsandtherapeuticeffectsofastragalosideivinslowtransitconstipation AT xingyangwan singlecellrnasequencingrevealscellulardynamicsandtherapeuticeffectsofastragalosideivinslowtransitconstipation AT qiulanhe singlecellrnasequencingrevealscellulardynamicsandtherapeuticeffectsofastragalosideivinslowtransitconstipation AT guozhongxiao singlecellrnasequencingrevealscellulardynamicsandtherapeuticeffectsofastragalosideivinslowtransitconstipation AT yihuizheng singlecellrnasequencingrevealscellulardynamicsandtherapeuticeffectsofastragalosideivinslowtransitconstipation AT minyiluo singlecellrnasequencingrevealscellulardynamicsandtherapeuticeffectsofastragalosideivinslowtransitconstipation AT chaoxinyang singlecellrnasequencingrevealscellulardynamicsandtherapeuticeffectsofastragalosideivinslowtransitconstipation AT donglinren singlecellrnasequencingrevealscellulardynamicsandtherapeuticeffectsofastragalosideivinslowtransitconstipation AT lilu singlecellrnasequencingrevealscellulardynamicsandtherapeuticeffectsofastragalosideivinslowtransitconstipation AT huipeng singlecellrnasequencingrevealscellulardynamicsandtherapeuticeffectsofastragalosideivinslowtransitconstipation AT hongchenglin singlecellrnasequencingrevealscellulardynamicsandtherapeuticeffectsofastragalosideivinslowtransitconstipation |