Potentiation of Collagen Deposition by the Combination of Substance P with Transforming Growth Factor Beta in Rat Skin Fibroblasts
A role for substance P has been proposed in musculoskeletal fibrosis, with effects mediated through transforming growth factor beta (TGFβ). We examined the in vitro effects of substance P on proliferation, collagen secretion, and collagen deposition in rat primary dermal fibroblasts cultured in medi...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
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MDPI AG
2024-02-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/25/3/1862 |
| _version_ | 1797318625354317824 |
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| author | Brendan A. Hilliard Mamta Amin Steven N. Popoff Mary F. Barbe |
| author_facet | Brendan A. Hilliard Mamta Amin Steven N. Popoff Mary F. Barbe |
| author_sort | Brendan A. Hilliard |
| collection | DOAJ |
| description | A role for substance P has been proposed in musculoskeletal fibrosis, with effects mediated through transforming growth factor beta (TGFβ). We examined the in vitro effects of substance P on proliferation, collagen secretion, and collagen deposition in rat primary dermal fibroblasts cultured in medium containing 10% fetal bovine serum, with or without TGFβ. In six-day cultures, substance P increased cell proliferation at concentrations from 0.0002 to 100 nM. TGFβ increased proliferation at concentrations from 0.0002 to 2 pg/mL, although higher concentrations inhibited proliferation. Substance P treatment alone at concentrations of 100, 0.2, and 0.00002 nM did not increase collagen deposition per cell, yet when combined with TGFβ (5 ng/mL), increased collagen deposition compared to TGFβ treatment alone. Substance P treatment (100 nM) also increased smooth muscle actin (SMA) expression at 72 h of culture at a level similar to 5 ng/mL of TGFβ; only TGFβ increased SMA at 48 h of culture. Thus, substance P may play a role in potentiating matrix deposition in vivo when combined with TGFβ, although this potentiation may be dependent on the concentration of each factor. Treatments targeting substance P may be a viable strategy for treating fibrosis where both substance P and TGFβ play roles. |
| first_indexed | 2024-03-08T03:55:02Z |
| format | Article |
| id | doaj.art-ce13f05e5bf4446b96e513d608a3a16b |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-08T03:55:02Z |
| publishDate | 2024-02-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-ce13f05e5bf4446b96e513d608a3a16b2024-02-09T15:14:54ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672024-02-01253186210.3390/ijms25031862Potentiation of Collagen Deposition by the Combination of Substance P with Transforming Growth Factor Beta in Rat Skin FibroblastsBrendan A. Hilliard0Mamta Amin1Steven N. Popoff2Mary F. Barbe3Aging and Cardiovascular Discovery Center, Lewis Katz School of Medicine at Temple University, Philadelphia, PA 19140, USAAging and Cardiovascular Discovery Center, Lewis Katz School of Medicine at Temple University, Philadelphia, PA 19140, USADepartment of Biomedical Education, Lewis Katz School of Medicine at Temple University, Philadelphia, PA 19140, USAAging and Cardiovascular Discovery Center, Lewis Katz School of Medicine at Temple University, Philadelphia, PA 19140, USAA role for substance P has been proposed in musculoskeletal fibrosis, with effects mediated through transforming growth factor beta (TGFβ). We examined the in vitro effects of substance P on proliferation, collagen secretion, and collagen deposition in rat primary dermal fibroblasts cultured in medium containing 10% fetal bovine serum, with or without TGFβ. In six-day cultures, substance P increased cell proliferation at concentrations from 0.0002 to 100 nM. TGFβ increased proliferation at concentrations from 0.0002 to 2 pg/mL, although higher concentrations inhibited proliferation. Substance P treatment alone at concentrations of 100, 0.2, and 0.00002 nM did not increase collagen deposition per cell, yet when combined with TGFβ (5 ng/mL), increased collagen deposition compared to TGFβ treatment alone. Substance P treatment (100 nM) also increased smooth muscle actin (SMA) expression at 72 h of culture at a level similar to 5 ng/mL of TGFβ; only TGFβ increased SMA at 48 h of culture. Thus, substance P may play a role in potentiating matrix deposition in vivo when combined with TGFβ, although this potentiation may be dependent on the concentration of each factor. Treatments targeting substance P may be a viable strategy for treating fibrosis where both substance P and TGFβ play roles.https://www.mdpi.com/1422-0067/25/3/1862substance pTGFbetafibroblastscollagenproliferationsmooth muscle actin |
| spellingShingle | Brendan A. Hilliard Mamta Amin Steven N. Popoff Mary F. Barbe Potentiation of Collagen Deposition by the Combination of Substance P with Transforming Growth Factor Beta in Rat Skin Fibroblasts International Journal of Molecular Sciences substance p TGFbeta fibroblasts collagen proliferation smooth muscle actin |
| title | Potentiation of Collagen Deposition by the Combination of Substance P with Transforming Growth Factor Beta in Rat Skin Fibroblasts |
| title_full | Potentiation of Collagen Deposition by the Combination of Substance P with Transforming Growth Factor Beta in Rat Skin Fibroblasts |
| title_fullStr | Potentiation of Collagen Deposition by the Combination of Substance P with Transforming Growth Factor Beta in Rat Skin Fibroblasts |
| title_full_unstemmed | Potentiation of Collagen Deposition by the Combination of Substance P with Transforming Growth Factor Beta in Rat Skin Fibroblasts |
| title_short | Potentiation of Collagen Deposition by the Combination of Substance P with Transforming Growth Factor Beta in Rat Skin Fibroblasts |
| title_sort | potentiation of collagen deposition by the combination of substance p with transforming growth factor beta in rat skin fibroblasts |
| topic | substance p TGFbeta fibroblasts collagen proliferation smooth muscle actin |
| url | https://www.mdpi.com/1422-0067/25/3/1862 |
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