2021 Fiscal Year Research-status Report
Defining the mechanism of epidermal stem cell heterogeneity in skin aging
| Project/Area Number |
20K22659
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| Research Institution | Kumamoto University |
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Principal Investigator |
Raja Erna 熊本大学, 国際先端医学研究機構, 特定事業研究員 (30770581)
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| Project Period (FY) |
2020-09-11 – 2023-03-31
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| Keywords | stem cells / ECM / aging |
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| Outline of Annual Research Achievements |
This study proposes that the slow- and fast-cycling epidermal stem cells undergo distinct process of aging which led to the identification of Fibulin 7 (F7) and its novel function in maintaining epidermal stem cell heterogeneity during skin aging. The loss of F7 led to premature depletion of the fast-cycling epidermal stem cells and delayed wound healing with increased epidermal stem cells inflammatory response genes and altered epidermal lineage specification genes.
Identification of F7 binding proteins indicated F7's roles in maintaining the basement membrane by binding to Collagen IV & Laminin and also during inflammatory response by binding to matricellular proteins such as tenascin C, periostin and CCDC80. Future study will address in more details F7 mechanism of action.
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| Current Status of Research Progress |
Current Status of Research Progress
2: Research has progressed on the whole more than it was originally planned.
Reason
The current study is now summarized and submitted for a publication, pending revision process.
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| Strategy for Future Research Activity |
Currently we aim to identify signaling pathway(s) that are relevant in mediating Fibulin 7 effects on epidermal stem cells homeostasis. A potential candidate is through modulation of Beta1-integrin receptor activity and its binding to other basement membrane proteins outside the cells or keratins intermediate filaments inside the cells. During wound healing, inflammatory pathways involving interleukins will be examined as well in the presence or absence of Fibulin 7. It is also interesting to study if Fibulin 7 or its binding proteins in protecting against skin inflammatory insults and the chronic effect in skin tumorigenesis.
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| Causes of Carryover |
To investigate further the mechanism of Fibulin 7 and its potential function in skin inflammation. The budget will be used for buying consumables related to biochemical experiments and imaging reagents and also for conference/travel expenses.
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