Application of FXYD3 protein or coding gene thereof as target spot in preparation of medicine for preventing and treating psoriasis

A technology that encodes genes and psoriasis, applied in the field of biomedicine, can solve problems such as unclear effects and specific mechanisms

Inactive Publication Date: 2022-05-10
ZHEJIANG UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

FXYD3 is mainly expressed in epithelial tissues such as gastrointestinal tract, skin, and pancreas, and studies have shown that FXYD3 plays a regulatory role in the occurrence and development of tumors (Zhu Z.L., Zhao Z.R., Zhang Y.H., Yang Y.H., Wang Z.M., Cui D.S., Wang M.W., Kleeff J., Kayed H., Yan B.Y. & Sun X.F. Expression and significance of FXYD-3 proteiningastricadenocarcinoma. Disease markers, 28:63-69(2010).), but the role of FXYD3 in skin homeostasis and psoriasis and its specific mechanism is unclear

Method used

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Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0029](1) Immunofluorescence detection of the expression of FXYD3 protein (GeneBank number: NP_032583.1) in the skin

[0030] Selected from outpatients of the Department of Dermatology of the Second Affiliated Hospital of Zhejiang University, with typical clinical manifestations of psoriasis patients (29 cases) (Human Research Ethics Committee of the Second Affiliated Hospital of Zhejiang University School of Medicine, project acceptance number: Research 2021-0268, event acceptance No.: IR2021001150), in which 2 cases of skin lesions were taken by conventional method and placed in normal saline, the samples were processed on the same day, and pathological sections were prepared; after paraffin sections were dewaxed, antigen retrieval was carried out with 0.01M (pH=6.0) sodium citrate; 3%H 2 o 2 Endogenous peroxidase was blocked, non-specific proteins were blocked with blocking solution; primary antibody (FXYD3 antibody, abcam, ab205534) was incubated overnight at 4°C, fluores...

Embodiment 2

[0035] (1) Preparation of skin lesion samples from patients with psoriasis

[0036] Selected from outpatients of the Department of Dermatology of the Second Affiliated Hospital of Zhejiang University, with typical clinical manifestations of psoriasis patients (29 cases) (Human Research Ethics Committee of the Second Affiliated Hospital of Zhejiang University School of Medicine, project acceptance number: Research 2021-0268, event acceptance No.: IR2021001150), wherein 29 cases of skin lesions and 16 cases of normal skin samples at the edge of skin lesions were placed in normal saline by conventional methods, and the samples were processed on the same day to prepare pathological sections. ).

[0037] (2) Immunohistochemical staining of human and mouse skin tissues

[0038] Human and mouse skin tissues were obtained, fixed in 10% formalin, embedded in paraffin within one week, and sectioned. The paraffin sections were placed in an oven at 67°C for 2 hours, dewaxed to water, an...

Embodiment 3

[0054] Construct transgenic mice with keratinocyte-specific knockout of the FXYD3 gene (as shown in SEQ ID No.21) through the Cre / loxp recombination system: FXYD3 flox / flox Mice with K14 cre The transgenic mice were cross-breeded, and after identification, the K14 cre FXYD3 flox / flox Mice were used as cKO experimental mice, littermate FXYD3 flox / flox Mice were used as WT experimental mice. Among them, FXYD3 flox / flox Mice and K14 cre The mice were all of C57BL / 6 background, purchased from Nanjing University-Nanjing Model Animal Center, and bred in the Experimental Animal Center of Zhejiang University.

[0055] (1) After IMQ was applied to the back skin of mice, back imaging was performed on 3 and 5 days. Psoriasis severity was assessed by mouse skin thickness, erythema, and scaling. Measure the mouse ear thickness with a caliper. Scale and erythema were scored on a scale of 0-4: 0, none; 1, mild; 2, moderate; 3, marked; 4, very marked.

[0056] (2) Skin sections were...

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PUM

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Abstract

The invention discloses application of FXYD3 protein or a coding gene thereof as a target spot in preparation of a medicine for preventing and treating psoriasis, and relates to the technical field of biological medicine. The invention finds that FXYD3 protein promotes the development of psoriasis, compared with a wild type (FXYD3flox / flox) mouse, an IMQ induced mouse psoriasis model has the advantages that the skin thickness, the scale and the epidermal thickness of an epidermal keratinocyte deleted FXYD3 (K14cre FXYD3flox / flox) mouse can be obviously reduced, the IL-17 signal and the expression of downstream chemotactic factors CXCL1 and CCL20 and antibacterial peptides S100A8 and S100A9 can be obviously reduced by deleting FXYD3 in keratinocytes, and the application of FXYD3 protein in inducing psoriasis in the mouse model has the advantages that the development of psoriasis is promoted; the immune cell infiltration is reduced, so that the psoriasis process is weakened. Therefore, the discovery of the invention indicates that the FXYD3 protein or the coding gene thereof can be used as a new action target for preventing and treating psoriasis.

Description

technical field [0001] The invention relates to the technical field of biomedicine, in particular to the application of FXYD3 protein or its coding gene as a target in the preparation of medicines for preventing and treating psoriasis. Background technique [0002] Psoriasis, commonly known as psoriasis, is a chronic skin disease characterized by a large number of inflammatory immune cell infiltration, abnormal thickening of the epidermis, and incomplete differentiation of keratin. According to statistics, the global incidence of psoriasis is about 1%-3%. It is recurrent and difficult to cure, which seriously affects the physical and mental health of patients and causes economic losses to individuals and society. A large number of clinical studies have shown that although psoriasis itself is not fatal, its complications include psoriatic arthritis, cardiovascular disease, diabetes, etc. These long-term complications may endanger the lives of patients. [0003] It is general...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K45/00A61K39/395A61K31/713A61P17/06
CPCA61K45/00A61K39/3955A61K31/713A61P17/06
Inventor 王青青来利华夏梦杨文娟连雯雯薛越潘婷
Owner ZHEJIANG UNIV
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