p53 and Myofibroblast Apoptosis in Organ Fibrosis
Organ fibrosis represents a dysregulated, maladaptive wound repair response that results in progressive disruption of normal tissue architecture leading to detrimental deterioration in physiological function, and significant morbidity/mortality. Fibrosis is thought to contribute to nearly 50% of all...
| Main Authors: | , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2023-04-01
|
| Series: | International Journal of Molecular Sciences |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1422-0067/24/7/6737 |
| _version_ | 1797607713241300992 |
|---|---|
| author | Kealan McElhinney Mustapha Irnaten Colm O’Brien |
| author_facet | Kealan McElhinney Mustapha Irnaten Colm O’Brien |
| author_sort | Kealan McElhinney |
| collection | DOAJ |
| description | Organ fibrosis represents a dysregulated, maladaptive wound repair response that results in progressive disruption of normal tissue architecture leading to detrimental deterioration in physiological function, and significant morbidity/mortality. Fibrosis is thought to contribute to nearly 50% of all deaths in the Western world with current treatment modalities effective in slowing disease progression but not effective in restoring organ function or reversing fibrotic changes. When physiological wound repair is complete, myofibroblasts are programmed to undergo cell death and self-clearance, however, in fibrosis there is a characteristic absence of myofibroblast apoptosis. It has been shown that in fibrosis, myofibroblasts adopt an apoptotic-resistant, highly proliferative phenotype leading to persistent myofibroblast activation and perpetuation of the fibrotic disease process. Recently, this pathological adaptation has been linked to dysregulated expression of tumour suppressor gene p53. In this review, we discuss p53 dysregulation and apoptotic failure in myofibroblasts and demonstrate its consistent link to fibrotic disease development in all types of organ fibrosis. An enhanced understanding of the role of p53 dysregulation and myofibroblast apoptosis may aid in future novel therapeutic and/or diagnostic strategies in organ fibrosis. |
| first_indexed | 2024-03-11T05:33:31Z |
| format | Article |
| id | doaj.art-2b25d101588c4bbdac663be7670ceb2b |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-11T05:33:31Z |
| publishDate | 2023-04-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-2b25d101588c4bbdac663be7670ceb2b2023-11-17T16:55:21ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-04-01247673710.3390/ijms24076737p53 and Myofibroblast Apoptosis in Organ FibrosisKealan McElhinney0Mustapha Irnaten1Colm O’Brien2UCD Clinical Research Centre, Mater Misericordiae University Hospital, D07 R2WY Dublin, IrelandUCD Clinical Research Centre, Mater Misericordiae University Hospital, D07 R2WY Dublin, IrelandUCD Clinical Research Centre, Mater Misericordiae University Hospital, D07 R2WY Dublin, IrelandOrgan fibrosis represents a dysregulated, maladaptive wound repair response that results in progressive disruption of normal tissue architecture leading to detrimental deterioration in physiological function, and significant morbidity/mortality. Fibrosis is thought to contribute to nearly 50% of all deaths in the Western world with current treatment modalities effective in slowing disease progression but not effective in restoring organ function or reversing fibrotic changes. When physiological wound repair is complete, myofibroblasts are programmed to undergo cell death and self-clearance, however, in fibrosis there is a characteristic absence of myofibroblast apoptosis. It has been shown that in fibrosis, myofibroblasts adopt an apoptotic-resistant, highly proliferative phenotype leading to persistent myofibroblast activation and perpetuation of the fibrotic disease process. Recently, this pathological adaptation has been linked to dysregulated expression of tumour suppressor gene p53. In this review, we discuss p53 dysregulation and apoptotic failure in myofibroblasts and demonstrate its consistent link to fibrotic disease development in all types of organ fibrosis. An enhanced understanding of the role of p53 dysregulation and myofibroblast apoptosis may aid in future novel therapeutic and/or diagnostic strategies in organ fibrosis.https://www.mdpi.com/1422-0067/24/7/6737fibrosisp53apoptosismyofibroblastextracellular matrixglaucoma |
| spellingShingle | Kealan McElhinney Mustapha Irnaten Colm O’Brien p53 and Myofibroblast Apoptosis in Organ Fibrosis International Journal of Molecular Sciences fibrosis p53 apoptosis myofibroblast extracellular matrix glaucoma |
| title | p53 and Myofibroblast Apoptosis in Organ Fibrosis |
| title_full | p53 and Myofibroblast Apoptosis in Organ Fibrosis |
| title_fullStr | p53 and Myofibroblast Apoptosis in Organ Fibrosis |
| title_full_unstemmed | p53 and Myofibroblast Apoptosis in Organ Fibrosis |
| title_short | p53 and Myofibroblast Apoptosis in Organ Fibrosis |
| title_sort | p53 and myofibroblast apoptosis in organ fibrosis |
| topic | fibrosis p53 apoptosis myofibroblast extracellular matrix glaucoma |
| url | https://www.mdpi.com/1422-0067/24/7/6737 |
| work_keys_str_mv | AT kealanmcelhinney p53andmyofibroblastapoptosisinorganfibrosis AT mustaphairnaten p53andmyofibroblastapoptosisinorganfibrosis AT colmobrien p53andmyofibroblastapoptosisinorganfibrosis |