Cell autonomous TLR4 signaling modulates TGF-β induced activation of human cardiac fibroblasts
Fibrosis is one of the major outcomes following injury in the heart. Immune response in the injury niche modulates fibrosis, yet little is known about how cell-autonomous immune signaling in adult cardiac fibroblasts regulates fibrosis. Using FACS, single-cell sequencing of cardiac fibroblasts from...
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| Format: | Article |
| Language: | English |
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Elsevier
2025-02-01
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| Series: | Heliyon |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2405844025008321 |
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| author | Gayathri Vijayakumar Anisha Latha Aiswaria P. Anil Yogini Surve Aiswarya R Bipin G. Nair Indulekha CL. Pillai |
| author_facet | Gayathri Vijayakumar Anisha Latha Aiswaria P. Anil Yogini Surve Aiswarya R Bipin G. Nair Indulekha CL. Pillai |
| author_sort | Gayathri Vijayakumar |
| collection | DOAJ |
| description | Fibrosis is one of the major outcomes following injury in the heart. Immune response in the injury niche modulates fibrosis, yet little is known about how cell-autonomous immune signaling in adult cardiac fibroblasts regulates fibrosis. Using FACS, single-cell sequencing of cardiac fibroblasts from Collagen1-α1GFP mice and human heart failure patients, we demonstrate that TLR4 is the major immune sensor expressed in cardiac fibroblasts. Inhibition of TLR4 signaling reduces TGF-β induced fibrotic changes such as contractibility and migration of adult human cardiac fibroblasts in TGF-β treated fibrotic conditions. TGF-β treated cardiac fibroblastss show enhanced cytokine expression, and inhibition of TLR4 signaling reduces the expression of cytokines, thereby reducing TGF-β targets such as extracellular matrix genes. Thus, our data demonstrate that TLR4 and other signaling molecules downstream of TLR4 are expressed in cardiac fibroblast, and inhibition of TLR4 modulates fibrotic changes in vitro. |
| format | Article |
| id | doaj-art-af5d278b6d564465b1f0d583a56d6ff9 |
| institution | Kabale University |
| issn | 2405-8440 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Heliyon |
| spelling | doaj-art-af5d278b6d564465b1f0d583a56d6ff92025-02-12T05:31:23ZengElsevierHeliyon2405-84402025-02-01114e42452Cell autonomous TLR4 signaling modulates TGF-β induced activation of human cardiac fibroblastsGayathri Vijayakumar0Anisha Latha1Aiswaria P. Anil2Yogini Surve3Aiswarya R4Bipin G. Nair5Indulekha CL. Pillai6Stem Cells and Regenerative Biology Lab, Amrita School of Biotechnology, Amrita Vishwa Vidyapeetham, Kollam, Kerala, IndiaStem Cells and Regenerative Biology Lab, Amrita School of Biotechnology, Amrita Vishwa Vidyapeetham, Kollam, Kerala, IndiaStem Cells and Regenerative Biology Lab, Amrita School of Biotechnology, Amrita Vishwa Vidyapeetham, Kollam, Kerala, IndiaStem Cells and Regenerative Biology Lab, Amrita School of Biotechnology, Amrita Vishwa Vidyapeetham, Kollam, Kerala, IndiaStem Cells and Regenerative Biology Lab, Amrita School of Biotechnology, Amrita Vishwa Vidyapeetham, Kollam, Kerala, IndiaAmrita School of Biotechnology, Amrita Vishwa Vidyapeetham, Kollam, Kerala, IndiaStem Cells and Regenerative Biology Lab, Amrita School of Biotechnology, Amrita Vishwa Vidyapeetham, Kollam, Kerala, India; Corresponding author. Stem cells and Regenerative Biology lab, Amrita School of Biotechnology, Amrita Vishwa Vidyapeetham, Clappana PO, Kollam, 690 525, Kerala, India.Fibrosis is one of the major outcomes following injury in the heart. Immune response in the injury niche modulates fibrosis, yet little is known about how cell-autonomous immune signaling in adult cardiac fibroblasts regulates fibrosis. Using FACS, single-cell sequencing of cardiac fibroblasts from Collagen1-α1GFP mice and human heart failure patients, we demonstrate that TLR4 is the major immune sensor expressed in cardiac fibroblasts. Inhibition of TLR4 signaling reduces TGF-β induced fibrotic changes such as contractibility and migration of adult human cardiac fibroblasts in TGF-β treated fibrotic conditions. TGF-β treated cardiac fibroblastss show enhanced cytokine expression, and inhibition of TLR4 signaling reduces the expression of cytokines, thereby reducing TGF-β targets such as extracellular matrix genes. Thus, our data demonstrate that TLR4 and other signaling molecules downstream of TLR4 are expressed in cardiac fibroblast, and inhibition of TLR4 modulates fibrotic changes in vitro.http://www.sciencedirect.com/science/article/pii/S2405844025008321 |
| spellingShingle | Gayathri Vijayakumar Anisha Latha Aiswaria P. Anil Yogini Surve Aiswarya R Bipin G. Nair Indulekha CL. Pillai Cell autonomous TLR4 signaling modulates TGF-β induced activation of human cardiac fibroblasts Heliyon |
| title | Cell autonomous TLR4 signaling modulates TGF-β induced activation of human cardiac fibroblasts |
| title_full | Cell autonomous TLR4 signaling modulates TGF-β induced activation of human cardiac fibroblasts |
| title_fullStr | Cell autonomous TLR4 signaling modulates TGF-β induced activation of human cardiac fibroblasts |
| title_full_unstemmed | Cell autonomous TLR4 signaling modulates TGF-β induced activation of human cardiac fibroblasts |
| title_short | Cell autonomous TLR4 signaling modulates TGF-β induced activation of human cardiac fibroblasts |
| title_sort | cell autonomous tlr4 signaling modulates tgf β induced activation of human cardiac fibroblasts |
| url | http://www.sciencedirect.com/science/article/pii/S2405844025008321 |
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