CN-121975908-A - Ultraviolet-induced skin injury marker and therapeutic drug

Abstract

The invention relates to the field of diagnosis and treatment of skin injury caused by ultraviolet rays, in particular to succinic dehydrogenase (Succinate dehydrogenase, SDH) serving as a marker of skin injury caused by ultraviolet rays and application of succinic dehydrogenase in preparation of therapeutic drugs. The ultraviolet irradiation leads to the obvious reduction of SDH activity in skin tissues and cells, thereby promoting the polarization of macrophages to M1 type and aggravating inflammatory reaction. By detecting SDH activity, it can be used as an effective marker for diagnosing and monitoring skin injury caused by ultraviolet rays. Over-expression of SDH subunit A or TRAP1 inhibitor DN401 can restore SDH activity, inhibit macrophage M1 polarization, and remarkably relieve skin erythema, edema, etc. caused by ultraviolet rays. The invention provides a new diagnosis and treatment strategy, effectively prevents and treats skin injury caused by ultraviolet rays by intervening SDH activity, and has remarkable clinical application prospect.

Inventors

• LI MIN
• CHEN XU
• CHEN YUJIE
• CHEN SIHAN
• LIAN NI

Assignees

• 中国医学科学院皮肤病医院(中国医学科学院皮肤病研究所)

Dates

Publication Date

20260505

Application Date

20260120

Claims (10)

1. 1. The application of succinate dehydrogenase as a marker for preparing skin injury caused by ultraviolet rays or the application of succinate dehydrogenase as an action target for regulating TRAP1 signaling pathway by a drug.
2. 2. The use according to claim 1, wherein in the ultraviolet-induced skin injury, macrophage M1 polarization ratio is increased and/or TRAP1 expression amount of skin tissue is increased.
3. 3. Use according to claim 2, characterized in that in uv-induced skin lesions the macrophage M1 polarization ratio is increased by at least 20% and/or the TRAP1 expression level is increased by at least 1.2 fold.
4. 4. The use according to claim 1, wherein the markers are used for diagnosing, monitoring or assessing qualitative and quantitative skin lesions.
5. 5. A cell model for diagnosing, monitoring or evaluating skin injury, characterized in that the cell model is a HaCaT cell and THP-1 cell co-culture model; a control group, namely inoculating the HaCaT cells, irradiating the HaCaT cells with ultraviolet rays, adding the THP-1 cells, co-culturing the THP-1 cells, collecting the THP-1 cells, and detecting the intracellular SDH activity; test group THP-1 cells were added and co-cultured to collect THP-1 cells and examine intracellular SDH activity.
6. 6. The use of a succinate dehydrogenase promoter for the manufacture of a medicament for the prevention and treatment of uv-induced skin damage.
7. 7. The use according to claim 6, wherein the promoter is capable of increasing SDH activity in THP-1 cells/macrophages and/or thereby inhibiting increases in the proportion of M1 polarization and TRAP1 expression.
8. 8. The method of claim 6, wherein the promoter is a gene editing agent, TRAP1 inhibitor, DN401, which promotes THP-1 cells/macrophages to enhance SDH activity.
9. Use of dn401 for the manufacture of a medicament for the treatment of skin damage caused by uv light.
10. 10. The use according to claim 9, wherein DN401 is an intradermal injection, topical application or oral formulation.

Description

Ultraviolet-induced skin injury marker and therapeutic drug Technical Field The invention relates to the field of diagnosis and treatment of skin injury caused by ultraviolet rays, in particular to a marker and a therapeutic drug of skin injury caused by ultraviolet rays. Background Ultraviolet radiation, particularly medium-wave Ultraviolet (UVB), is a major environmental factor causing acute skin injury (sunburn) or even skin tumors. According to the consensus of the dermatological community, uv-induced skin damage is a pathological lineage ranging from acute sunburn to chronic cumulative damage represented by photoaging and photo-carcinogenesis (collectively photo-damage, photodamage). The root cause is direct and indirect damage to skin cell DNA, oxidative stress systems, and connective tissue by uv light. Histopathologically, sunburn is marked by sunburn cells (i.e. apoptotic keratinocytes) accompanied by infiltration of acute inflammatory cells of dermis, and chronic photodamage is characterized by irregular hyperplasia and atrophy of epidermis, chronic inflammation of dermis, elastosis, etc. Recent studies have revealed that the innate immune system is central in the process of uv-induced skin damage. Among them, macrophages, which are key inflammatory regulatory cells, are recruited and polarized to the pro-inflammatory M1 phenotype after uv irradiation, and maintain and amplify the inflammatory cascade by releasing factors such as TNF- α, IL-1β, etc., are key to causing the duration of clinical symptoms. Thus, uv-induced skin damage is a dynamic inflammatory process that is dominated by immune cells. Based on this, inhibition of hyperpolarization of macrophages to M1 is considered as a very potential new therapeutic strategy for alleviating uv-induced skin damage. However, currently the mainstay of clinical therapy, topical glucocorticoids, exert a "downstream" interceptive effect mainly through broad-spectrum inhibition of inflammatory mediators. Although the symptom can be relieved, the long-term use of the traditional Chinese medicine composition is easy to cause side effects such as skin atrophy, telangiectasia and the like, and the immune process of M1 polarization cannot be interfered from the source or the inside of macrophages. Therefore, there is a strong need in the art to develop more efficient and safer sunburn protection and treatment means that can precisely regulate the skin immune microenvironment, inhibit macrophage M1 polarization from the "upstream" source, and subsequent inflammatory outbreaks. The innovation of this therapeutic strategy relies on a deep understanding of the leading field of "immune metabolism". The tricarboxylic acid cycle is a central element of eukaryotic cell energy metabolism, whose function is decisive for the activation and differentiation of immune cells. Specifically, activation of M1-type macrophages is closely related to its unique metabolic pattern, including the breakdown of the tricarboxylic acid cycle (Tricarboxylic ACID CYCLE, TCA) and the accumulation of specific metabolites. The succinic acid dehydrogenase (Succinate Dehydrogenase, SDH) is used as a key enzyme in the TCA cycle and is responsible for catalyzing succinic acid into fumaric acid, the activity of the succinic acid dehydrogenase directly influences the level of key metabolites such as intracellular succinic acid, and the metabolites can be used as signal molecules to directly participate in regulating and controlling the expression of inflammation related genes and the production of cytokines, so that the TCA key enzyme such as SDH becomes a junction for connecting the metabolism and the immune function of cells. Although the importance of SDH in immune metabolism is increasingly highlighted, no research has yet revealed that it is involved in the UV-induced skin injury process by modulating macrophage polarization. The technical proposal is that the M1 polarization of the macrophage is specifically inhibited by intervening the activity or the function of the enzyme, so that the ultraviolet-induced skin injury and inflammatory reaction are reversed, and the ultraviolet-induced skin injury and inflammatory reaction are used for preventing or treating photoinjury. Disclosure of Invention It is an object of the present invention to provide a novel use of succinate dehydrogenase which provides a novel idea for the prevention and treatment of skin damage caused by ultraviolet light. In order to achieve the above purpose, the technical scheme of the invention is as follows: The application of succinate dehydrogenase as a marker for preparing skin injury caused by ultraviolet rays or the application of succinate dehydrogenase as an action target for regulating TRAP1 signaling pathway by a drug. Succinate dehydrogenase (Succinate Dehydrogenase, SDH) has an important biomarker role in uv-induced skin damage. SDH is a key enzyme in the tricarboxylic acid cycle responsible for catalyzing succin