Cargando…

TGF-β1 upregulates Sar1a expression and induces procollagen-I secretion in hypertrophic scarring fibroblasts

Hypertrophic scarring (HTS) is a common fibroproliferative disorder that typically follows thermal and other injuries involving the deep dermis. The underlying pathogenic mechanisms are regulated by transforming growth factor-β (TGF-β); however, the exact mechanisms in HTS have not been elucidated....

Descripción completa

Detalles Bibliográficos
Autores principales: Ahn, Keun Jae, Kim, Jun-Sub
Formato: Online Artículo Texto
Lenguaje:English
Publicado: De Gruyter 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9483117/
https://www.ncbi.nlm.nih.gov/pubmed/36188194
http://dx.doi.org/10.1515/med-2022-0543
_version_ 1784791604860551168
author Ahn, Keun Jae
Kim, Jun-Sub
author_facet Ahn, Keun Jae
Kim, Jun-Sub
author_sort Ahn, Keun Jae
collection PubMed
description Hypertrophic scarring (HTS) is a common fibroproliferative disorder that typically follows thermal and other injuries involving the deep dermis. The underlying pathogenic mechanisms are regulated by transforming growth factor-β (TGF-β); however, the exact mechanisms in HTS have not been elucidated. We conducted this study to explore the cellular signaling mechanisms for expression of Sar1a, a coat protein complex II-associated small GTPase, in HTS fibroblasts (HTSF). We found that Sar1a was upregulated in HTSF as compared to that in normal fibroblasts. Furthermore, stimulation of TGF-β1 increased the expression of Sar1a in HTSF, and small interfering RNA for Sar1a suppressed procollagen-I (PC-I) secretion. Next we investigated the signaling mechanism from TGF-β1 to Sar1a expression and its association with PC-I secretion. In the presence of TGF-β-activated kinase 1 (TAK1), c-Jun N-terminal kinase, or p38 inhibitors, the effect of TGF-β1 on Sar1a expression and PC-I secretion significantly decreased; however, it had no effect on collagen-1A (Col-1A) expression. Further, the inhibitors of Smad3 or extracellular signal-regulated kinases inhibited TGF-β1-induced Col-1A expression but had no effect on PC-I secretion and Sar1a expression. Taken together, our results suggested that TGF-β1 induces Sar1a expression through TAK1 signaling and this signaling event regulates PC-I secretion in HTSF.
format Online
Article
Text
id pubmed-9483117
institution National Center for Biotechnology Information
language English
publishDate 2022
publisher De Gruyter
record_format MEDLINE/PubMed
spelling pubmed-94831172022-10-01 TGF-β1 upregulates Sar1a expression and induces procollagen-I secretion in hypertrophic scarring fibroblasts Ahn, Keun Jae Kim, Jun-Sub Open Med (Wars) Research Article Hypertrophic scarring (HTS) is a common fibroproliferative disorder that typically follows thermal and other injuries involving the deep dermis. The underlying pathogenic mechanisms are regulated by transforming growth factor-β (TGF-β); however, the exact mechanisms in HTS have not been elucidated. We conducted this study to explore the cellular signaling mechanisms for expression of Sar1a, a coat protein complex II-associated small GTPase, in HTS fibroblasts (HTSF). We found that Sar1a was upregulated in HTSF as compared to that in normal fibroblasts. Furthermore, stimulation of TGF-β1 increased the expression of Sar1a in HTSF, and small interfering RNA for Sar1a suppressed procollagen-I (PC-I) secretion. Next we investigated the signaling mechanism from TGF-β1 to Sar1a expression and its association with PC-I secretion. In the presence of TGF-β-activated kinase 1 (TAK1), c-Jun N-terminal kinase, or p38 inhibitors, the effect of TGF-β1 on Sar1a expression and PC-I secretion significantly decreased; however, it had no effect on collagen-1A (Col-1A) expression. Further, the inhibitors of Smad3 or extracellular signal-regulated kinases inhibited TGF-β1-induced Col-1A expression but had no effect on PC-I secretion and Sar1a expression. Taken together, our results suggested that TGF-β1 induces Sar1a expression through TAK1 signaling and this signaling event regulates PC-I secretion in HTSF. De Gruyter 2022-09-17 /pmc/articles/PMC9483117/ /pubmed/36188194 http://dx.doi.org/10.1515/med-2022-0543 Text en © 2022 Keun Jae Ahn and Jun-Sub Kim, published by De Gruyter https://creativecommons.org/licenses/by/4.0/This work is licensed under the Creative Commons Attribution 4.0 International License.
spellingShingle Research Article
Ahn, Keun Jae
Kim, Jun-Sub
TGF-β1 upregulates Sar1a expression and induces procollagen-I secretion in hypertrophic scarring fibroblasts
title TGF-β1 upregulates Sar1a expression and induces procollagen-I secretion in hypertrophic scarring fibroblasts
title_full TGF-β1 upregulates Sar1a expression and induces procollagen-I secretion in hypertrophic scarring fibroblasts
title_fullStr TGF-β1 upregulates Sar1a expression and induces procollagen-I secretion in hypertrophic scarring fibroblasts
title_full_unstemmed TGF-β1 upregulates Sar1a expression and induces procollagen-I secretion in hypertrophic scarring fibroblasts
title_short TGF-β1 upregulates Sar1a expression and induces procollagen-I secretion in hypertrophic scarring fibroblasts
title_sort tgf-β1 upregulates sar1a expression and induces procollagen-i secretion in hypertrophic scarring fibroblasts
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9483117/
https://www.ncbi.nlm.nih.gov/pubmed/36188194
http://dx.doi.org/10.1515/med-2022-0543
work_keys_str_mv AT ahnkeunjae tgfb1upregulatessar1aexpressionandinducesprocollagenisecretioninhypertrophicscarringfibroblasts
AT kimjunsub tgfb1upregulatessar1aexpressionandinducesprocollagenisecretioninhypertrophicscarringfibroblasts