HSP47 Increases the Expression of Type I Collagen in Fibroblasts through IRE1α Activation, XBP1 Splicing, and Nuclear Translocation of β-Catenin
Heat shock protein 47 (HSP47), also known as <i>SERPINH1</i>, functions as a collagen-specific molecular chaperone protein essential for the formation and stabilization of the collagen triple helix. Here, we delved into the regulatory pathways governed by HSP47, shedding light on collage...
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MDPI AG
2024-03-01
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| Series: | Cells |
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| Online Access: | https://www.mdpi.com/2073-4409/13/6/527 |
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| author | So Young Ham Min Ju Pyo Moonkyung Kang Yeon-Soo Kim Dong Hun Lee Jin Ho Chung Seung-Taek Lee |
| author_facet | So Young Ham Min Ju Pyo Moonkyung Kang Yeon-Soo Kim Dong Hun Lee Jin Ho Chung Seung-Taek Lee |
| author_sort | So Young Ham |
| collection | DOAJ |
| description | Heat shock protein 47 (HSP47), also known as <i>SERPINH1</i>, functions as a collagen-specific molecular chaperone protein essential for the formation and stabilization of the collagen triple helix. Here, we delved into the regulatory pathways governed by HSP47, shedding light on collagen homeostasis. Our investigation revealed a significant reduction in <i>HSP47</i> mRNA levels in the skin tissue of older mice as compared to their younger counterparts. The augmented expression of HSP47 employing lentivirus infection in fibroblasts resulted in an increased secretion of type I collagen. Intriguingly, the elevated expression of HSP47 in fibroblasts correlated with increased protein and mRNA levels of type I collagen. The exposure of fibroblasts to IRE1α RNase inhibitors resulted in the reduced manifestation of HSP47-induced type I collagen secretion and expression. Notably, HSP47-overexpressing fibroblasts exhibited increased <i>XBP1</i> mRNA splicing. The overexpression of HSP47 or spliced XBP1 facilitated the nuclear translocation of β-catenin and transactivated a reporter harboring TCF binding sites on the promoter. Furthermore, the overexpression of HSP47 or spliced XBP1 or the augmentation of nuclear β-catenin through Wnt3a induced the expression of type I collagen. Our findings substantiate that HSP47 enhances type I collagen expression and secretion in fibroblasts by orchestrating a mechanism that involves an increase in nuclear β-catenin through IRE1α activation and XBP1 splicing. This study therefore presents potential avenues for an anti-skin-aging strategy targeting HSP47-mediated processes. |
| first_indexed | 2024-04-24T18:26:34Z |
| format | Article |
| id | doaj.art-2f2605b77da3487e96be4c22fdb28006 |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-04-24T18:26:34Z |
| publishDate | 2024-03-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-2f2605b77da3487e96be4c22fdb280062024-03-27T13:30:40ZengMDPI AGCells2073-44092024-03-0113652710.3390/cells13060527HSP47 Increases the Expression of Type I Collagen in Fibroblasts through IRE1α Activation, XBP1 Splicing, and Nuclear Translocation of β-CateninSo Young Ham0Min Ju Pyo1Moonkyung Kang2Yeon-Soo Kim3Dong Hun Lee4Jin Ho Chung5Seung-Taek Lee6Department of Biochemistry, College of Life Science and Biotechnology, Yonsei University, Seoul 03722, Republic of KoreaDepartment of Biochemistry, College of Life Science and Biotechnology, Yonsei University, Seoul 03722, Republic of KoreaR&D Center, artiCure Inc., Daejeon 34134, Republic of KoreaR&D Center, artiCure Inc., Daejeon 34134, Republic of KoreaDepartment of Dermatology, Seoul National University College of Medicine, Seoul 03080, Republic of KoreaDepartment of Dermatology, Seoul National University College of Medicine, Seoul 03080, Republic of KoreaDepartment of Biochemistry, College of Life Science and Biotechnology, Yonsei University, Seoul 03722, Republic of KoreaHeat shock protein 47 (HSP47), also known as <i>SERPINH1</i>, functions as a collagen-specific molecular chaperone protein essential for the formation and stabilization of the collagen triple helix. Here, we delved into the regulatory pathways governed by HSP47, shedding light on collagen homeostasis. Our investigation revealed a significant reduction in <i>HSP47</i> mRNA levels in the skin tissue of older mice as compared to their younger counterparts. The augmented expression of HSP47 employing lentivirus infection in fibroblasts resulted in an increased secretion of type I collagen. Intriguingly, the elevated expression of HSP47 in fibroblasts correlated with increased protein and mRNA levels of type I collagen. The exposure of fibroblasts to IRE1α RNase inhibitors resulted in the reduced manifestation of HSP47-induced type I collagen secretion and expression. Notably, HSP47-overexpressing fibroblasts exhibited increased <i>XBP1</i> mRNA splicing. The overexpression of HSP47 or spliced XBP1 facilitated the nuclear translocation of β-catenin and transactivated a reporter harboring TCF binding sites on the promoter. Furthermore, the overexpression of HSP47 or spliced XBP1 or the augmentation of nuclear β-catenin through Wnt3a induced the expression of type I collagen. Our findings substantiate that HSP47 enhances type I collagen expression and secretion in fibroblasts by orchestrating a mechanism that involves an increase in nuclear β-catenin through IRE1α activation and XBP1 splicing. This study therefore presents potential avenues for an anti-skin-aging strategy targeting HSP47-mediated processes.https://www.mdpi.com/2073-4409/13/6/527HSP47fibroblasttype I collagenextracellular matrixskin aging |
| spellingShingle | So Young Ham Min Ju Pyo Moonkyung Kang Yeon-Soo Kim Dong Hun Lee Jin Ho Chung Seung-Taek Lee HSP47 Increases the Expression of Type I Collagen in Fibroblasts through IRE1α Activation, XBP1 Splicing, and Nuclear Translocation of β-Catenin Cells HSP47 fibroblast type I collagen extracellular matrix skin aging |
| title | HSP47 Increases the Expression of Type I Collagen in Fibroblasts through IRE1α Activation, XBP1 Splicing, and Nuclear Translocation of β-Catenin |
| title_full | HSP47 Increases the Expression of Type I Collagen in Fibroblasts through IRE1α Activation, XBP1 Splicing, and Nuclear Translocation of β-Catenin |
| title_fullStr | HSP47 Increases the Expression of Type I Collagen in Fibroblasts through IRE1α Activation, XBP1 Splicing, and Nuclear Translocation of β-Catenin |
| title_full_unstemmed | HSP47 Increases the Expression of Type I Collagen in Fibroblasts through IRE1α Activation, XBP1 Splicing, and Nuclear Translocation of β-Catenin |
| title_short | HSP47 Increases the Expression of Type I Collagen in Fibroblasts through IRE1α Activation, XBP1 Splicing, and Nuclear Translocation of β-Catenin |
| title_sort | hsp47 increases the expression of type i collagen in fibroblasts through ire1α activation xbp1 splicing and nuclear translocation of β catenin |
| topic | HSP47 fibroblast type I collagen extracellular matrix skin aging |
| url | https://www.mdpi.com/2073-4409/13/6/527 |
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