Cyclic Adenosine Monophosphate Eliminates Sex Differences in Estradiol-Induced Elastin Production from Engineered Dermal Substitutes
Lack of adult cells’ ability to produce sufficient amounts of elastin and assemble functional elastic fibers is an issue for creating skin substitutes that closely match native skin properties. The effects of female sex hormones, primarily estrogen, have been studied due to the known effects on elas...
| Main Authors: | , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2021-06-01
|
| Series: | International Journal of Molecular Sciences |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1422-0067/22/12/6358 |
| _version_ | 1797530189863845888 |
|---|---|
| author | Andreja Moset Zupan Carolyn Nietupski Stacey C. Schutte |
| author_facet | Andreja Moset Zupan Carolyn Nietupski Stacey C. Schutte |
| author_sort | Andreja Moset Zupan |
| collection | DOAJ |
| description | Lack of adult cells’ ability to produce sufficient amounts of elastin and assemble functional elastic fibers is an issue for creating skin substitutes that closely match native skin properties. The effects of female sex hormones, primarily estrogen, have been studied due to the known effects on elastin post-menopause, thus have primarily included older mostly female populations. In this study, we examined the effects of female sex hormones on the synthesis of elastin by female and male human dermal fibroblasts in engineered dermal substitutes. Differences between the sexes were observed with 17β-estradiol treatment alone stimulating elastin synthesis in female substitutes but not male. TGF-β levels were significantly higher in male dermal substitutes than female dermal substitutes and the levels did not change with 17β-estradiol treatment. The male dermal substitutes had a 1.5-fold increase in cAMP concentration in the presence of 17β-estradiol compared to no hormone controls, while cAMP concentrations remained constant in the female substitutes. When cAMP was added in addition to 17β-estradiol and progesterone in the culture medium, the sex differences were eliminated, and elastin synthesis was upregulated by 2-fold in both male and female dermal substitutes. These conditions alone did not result in functionally significant amounts of elastin or complete elastic fibers. The findings presented provide insights into differences between male and female cells in response to female sex steroid hormones and the involvement of the cAMP pathway in elastin synthesis. Further explorations into the signaling pathways may identify better targets to promote elastic fiber synthesis in skin substitutes. |
| first_indexed | 2024-03-10T10:25:28Z |
| format | Article |
| id | doaj.art-752008d7571945429e69fa7a52d407c3 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T10:25:28Z |
| publishDate | 2021-06-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-752008d7571945429e69fa7a52d407c32023-11-22T00:05:03ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-06-012212635810.3390/ijms22126358Cyclic Adenosine Monophosphate Eliminates Sex Differences in Estradiol-Induced Elastin Production from Engineered Dermal SubstitutesAndreja Moset Zupan0Carolyn Nietupski1Stacey C. Schutte2Department of Biomedical Engineering, University of Cincinnati, Cincinnati, OH 45221, USADepartment of Biomedical Engineering, University of Cincinnati, Cincinnati, OH 45221, USADepartment of Biomedical Engineering, University of Cincinnati, Cincinnati, OH 45221, USALack of adult cells’ ability to produce sufficient amounts of elastin and assemble functional elastic fibers is an issue for creating skin substitutes that closely match native skin properties. The effects of female sex hormones, primarily estrogen, have been studied due to the known effects on elastin post-menopause, thus have primarily included older mostly female populations. In this study, we examined the effects of female sex hormones on the synthesis of elastin by female and male human dermal fibroblasts in engineered dermal substitutes. Differences between the sexes were observed with 17β-estradiol treatment alone stimulating elastin synthesis in female substitutes but not male. TGF-β levels were significantly higher in male dermal substitutes than female dermal substitutes and the levels did not change with 17β-estradiol treatment. The male dermal substitutes had a 1.5-fold increase in cAMP concentration in the presence of 17β-estradiol compared to no hormone controls, while cAMP concentrations remained constant in the female substitutes. When cAMP was added in addition to 17β-estradiol and progesterone in the culture medium, the sex differences were eliminated, and elastin synthesis was upregulated by 2-fold in both male and female dermal substitutes. These conditions alone did not result in functionally significant amounts of elastin or complete elastic fibers. The findings presented provide insights into differences between male and female cells in response to female sex steroid hormones and the involvement of the cAMP pathway in elastin synthesis. Further explorations into the signaling pathways may identify better targets to promote elastic fiber synthesis in skin substitutes.https://www.mdpi.com/1422-0067/22/12/6358elastindermal fibroblastsestrogencAMPtissue engineering |
| spellingShingle | Andreja Moset Zupan Carolyn Nietupski Stacey C. Schutte Cyclic Adenosine Monophosphate Eliminates Sex Differences in Estradiol-Induced Elastin Production from Engineered Dermal Substitutes International Journal of Molecular Sciences elastin dermal fibroblasts estrogen cAMP tissue engineering |
| title | Cyclic Adenosine Monophosphate Eliminates Sex Differences in Estradiol-Induced Elastin Production from Engineered Dermal Substitutes |
| title_full | Cyclic Adenosine Monophosphate Eliminates Sex Differences in Estradiol-Induced Elastin Production from Engineered Dermal Substitutes |
| title_fullStr | Cyclic Adenosine Monophosphate Eliminates Sex Differences in Estradiol-Induced Elastin Production from Engineered Dermal Substitutes |
| title_full_unstemmed | Cyclic Adenosine Monophosphate Eliminates Sex Differences in Estradiol-Induced Elastin Production from Engineered Dermal Substitutes |
| title_short | Cyclic Adenosine Monophosphate Eliminates Sex Differences in Estradiol-Induced Elastin Production from Engineered Dermal Substitutes |
| title_sort | cyclic adenosine monophosphate eliminates sex differences in estradiol induced elastin production from engineered dermal substitutes |
| topic | elastin dermal fibroblasts estrogen cAMP tissue engineering |
| url | https://www.mdpi.com/1422-0067/22/12/6358 |
| work_keys_str_mv | AT andrejamosetzupan cyclicadenosinemonophosphateeliminatessexdifferencesinestradiolinducedelastinproductionfromengineereddermalsubstitutes AT carolynnietupski cyclicadenosinemonophosphateeliminatessexdifferencesinestradiolinducedelastinproductionfromengineereddermalsubstitutes AT staceycschutte cyclicadenosinemonophosphateeliminatessexdifferencesinestradiolinducedelastinproductionfromengineereddermalsubstitutes |