CN120586057A - Application of METTL1 as a target in the preparation of drugs for the treatment of erythematous and scaly skin diseases - Google Patents

Abstract

The invention discloses an application of METTL as a target in preparing a medicament for treating erythema and scaling skin diseases, relates to the field of biological medicines, provides a new scheme for treating the erythema and scaling skin diseases, especially psoriasis and atopic dermatitis, and reduces erythema, scaling and skin thickness by inhibiting METTL1 expression so as to further reduce inflammatory reaction of the psoriasis or the atopic dermatitis.

Description

Application of METTL A as target in preparation of medicine for treating erythema scale skin disease

Technical Field

The invention relates to the technical field of biological medicines, in particular to application of METTL serving as a target spot in preparation of a medicine for treating erythema scale skin diseases.

Background

Psoriasis and atopic dermatitis are two common chronic inflammatory skin diseases of the dermatological family, and belong to immune-mediated chronic, recurrent, inflammatory and systemic diseases under the combined action of genetic and environmental factors. The pathogenesis of psoriasis is mainly related to abnormal immune response mediated by T cells, and especially Th17 cells and cytokines secreted by the Th17 cells (such as IL-17, IL-23 and the like) play a central role in the pathogenesis of psoriasis. Atopic dermatitis is mediated mainly by Th2 cells and is characterized by dysfunctional skin barriers and abnormal immune response, manifested by dry skin, itching and inflammation.

In particular, the pathogenesis of psoriasis is mainly related to abnormal T cell mediated immune responses, and in particular Th17 cells and their secreted cytokines (e.g. IL-17, IL-23, etc.) play a central role in the pathogenesis of psoriasis. Current methods of treatment mainly include topical treatments (e.g., glucocorticoids, vitamin D3 analogs, etc.) and systemic treatments (e.g., biologies, immunosuppressants, etc.). However, these treatments have certain limitations, such as limited effectiveness of topical treatments and serious side effects of systemic treatments. Whereas the pathogenesis of atopic dermatitis is mainly related to Th2 cell-mediated immune responses and skin barrier dysfunction. Methods of treatment include topical administration of glucocorticoids and calcineurin inhibitors, as well as systemic treatment (e.g., biologicals, etc.), and existing methods of treatment remain inadequate in terms of controlling the condition and alleviating symptoms.

Although there is a certain understanding of the immune pathogenesis of psoriasis and atopic dermatitis, the interactions of various immune cells and cytokines are involved, and the specific molecular mechanisms have not yet been fully elucidated. In addition, the existing treatment methods still have certain limitations in terms of controlling the illness state and relieving symptoms, and the expected treatment effect cannot be achieved. Therefore, research is focused on deeply analyzing the disease mechanism and developing more accurate and safer treatment strategies to increase the treatment effect and improve the quality of life of patients.

Disclosure of Invention

In view of the above problems, the present invention provides novel targets and drugs for treating psoriasis or atopic dermatitis

In order to achieve the above object, the present invention provides the following technical solutions:

Use of METTL a as a target in the development, screening and/or manufacture of a medicament for the treatment of erythema-scaling skin disorders.

Preferably, the target is used in the development, screening and/or preparation of a medicament for the treatment of psoriasis.

Preferably, the target is used in the development, screening and/or preparation of a medicament for the treatment of atopic dermatitis.

The invention also discloses application of METTL a inhibitor in preparation of a medicament for treating erythema scale skin diseases.

Preferably, the METTL inhibitor is used for preparing a medicament for treating psoriasis.

Preferably, the METTL inhibitor is used for preparing a medicament for treating atopic dermatitis.

Further, the METTL inhibitor is at least one of a monoclonal antibody, a small molecule compound, or a nucleic acid inhibitor that specifically inhibits METTL1 activity.

The small molecular compound IN METTL A inhibitor can be METTL-WDR 4-IN-1, and has chemical formula of C ₈H₁₁N₅O₂ S and molecular weight of 241.27.

The nucleic acid inhibitor in METTL inhibitor may be an siRNA sequence, which is as follows:

Because the in vivo environment is complex, in order to improve the stability of siRNA, 2-OMe modification is carried out on ribose 2 position of full-strand RNA base, 2-OMe modification is not needed for protecting base at 3 end, and simultaneously, cholesterol modification is carried out on the end of siRNA in order to promote the siRNA to enter cells in vivo, and the cholesterol modification is carried out at 3 end of siRNA sense strand.

SiRNA sequence 1:

The sense strand of siRNA sequence 1 is CCCACACUUUAAGCGAACGAATT, and the antisense strand of siRNA sequence 1 is UUCGUUCGCUUAAAGUGUGGGTT;

Modified SiRNA sequence 1:

sense strand CCCACACUUUAAGCGAACGAAdTdT and antisense strand UUCGUUCGCUUAAAGUGUGGGdTdT.

SiRNA sequence 2:

the sense strand of siRNA sequence 2 is GAUGACCCAAAGGAUAAGAAATT, and the antisense strand of siRNA sequence 2 is UUUCUUAUCCUUUGGGUCAUCTT;

The modified SiRNA sequence 2 is:

Sense strand GAUGACCCAAAGGAUAAGAAAdTdT and antisense strand UUUCUUAUCCUUUGGGUCAUCdTdT.

METTL1 inhibitor can inhibit keratinocyte proliferation and immune response by inhibiting METTL1 methylation modification enzyme activity, and remarkably relieve mouse ear inflammatory reaction, and further relieve psoriasis and atopic dermatitis morbidity.

Of course, the medicament also comprises pharmaceutically acceptable auxiliary materials.

The medicine can be prepared into any one of injection, patch, powder, tablet, capsule, gel or paste. Preferably, the composition is prepared into external medicines such as cream, liniment and spray.

If the cream is prepared, the cream can be combined with common cream matrixes such as vaseline, if the liniment can be combined with substances such as sodium alginate, hyaluronic acid, glycerol, and the like, if the spray can be mixed with substances such as water, propylene glycol, and the like.

Preferably, METTL-WDR 4-IN-1 is formulated to ensure a drug concentration of 5mM or more.

The beneficial effects are that:

METTL 1A can be used as a therapeutic target for erythema scale skin diseases, especially psoriasis and atopic dermatitis. After METTL of 1-WDR4-IN-1 inhibitor and siRNA sequence are used for inhibiting target METTL1, the inflammation of the ears of the mice is obviously reduced, and the reduction of erythema, scales and skin thickness is shown, which shows that the small molecular compound METTL-WDR 4-IN-1 and siRNA sequence as METTL1 inhibitor has positive therapeutic significance on psoriasis and atopic dermatitis as well as erythema-scaling skin diseases. Meanwhile, METTL-WDR 4-IN-1 and siRNA can be prepared into external cream IN the treatment process, and the operation is simple and the implementation is easy.

Drawings

FIG. 1 shows immunofluorescent staining of METL1 in healthy human skin, psoriasis and atopic dermatitis patients;

FIG. 2 is a schematic representation of the chemical formula METL1-WDR 4-IN-1;

FIG. 3 screening for optimal working concentration of drug using HaCaT cells;

FIG. 4 is a photograph of ear of METL1-WDR 4-IN-1 treated IMQ mice;

FIG. 5 shows PASI score and ear thickness plots after IMQ mice treatment;

FIG. 6 downstream inflammatory factor qRT-PCR detection after IMQ mice treatment;

FIG. 7 is a photograph of an ear of a METL1-WDR 4-IN-1 treated atopic dermatitis mouse;

FIG. 8 shows a score plot and an ear thickness plot of SCORAD after treatment of atopic dermatitis mice;

FIG. 9 downstream inflammatory factor qRT-PCR detection after atopic dermatitis mice treatment;

FIG. 10 ear pictures of METL1 siRNA sequence 1 in treating IMQ mice;

FIG. 11 shows PASI score and ear thickness plots after IMQ mice treatment;

FIG. 12 downstream inflammatory factor qRT-PCR detection after IMQ mice treatment;

FIG. 13 is a photograph of ears of METL1 siRNA sequence 1 in a mouse for treating atopic dermatitis;

FIG. 14 shows PASI score and ear thickness plots after treatment of atopic dermatitis mice;

FIG. 15 downstream inflammatory factor qRT-PCR detection after atopic dermatitis mice treatment;

FIG. 16 is a diagram of a simulated psoriasis cell dish distribution using the HaCaT cell line;

FIG. 17 is a diagram of a simulated atopic dermatitis cell tray distribution using the HaCaT cell line;

FIG. 18 downstream inflammatory factor qRT-PCR detection after treatment of psoriasis cell model with METTL1 siRNA sequence 2;

FIG. 19 downstream inflammatory factor qRT-PCR detection after treatment of atopic dermatitis cell model with METTL siRNA sequence 2.

Detailed Description

The invention will be described in detail below with reference to specific embodiments and accompanying drawings:

EXAMPLE 1 upregulation of METL1 expression in skin lesions in psoriasis and atopic dermatitis patients

Immunofluorescent staining was performed on skin sections of healthy controls and psoriasis patients, and atopic dermatitis patients. The results obtained are shown in FIG. 1. The results according to fig. 1 show that METTL a is highly expressed in skin tissue of psoriasis patients and atopic dermatitis patients compared to healthy skin tissue, suggesting that METTL a may be involved in the pathogenesis of psoriasis and atopic dermatitis.

EXAMPLE 2 METL1 inhibitor METTL1-WDR4-IN-1

The METTL-WDR 4-IN-1 adopted by the invention has a chemical formula of C ₈H₁₁N₅O₂ S, a molecular weight of 241.27, and is purchased from MCE (374705-10-9), and a specific structure is shown IN figure 2.

The optimal working concentration of METTL-WDR 4-IN-1 was selected using HaCaT cells and the results obtained are shown IN FIG. 3. As is clear from the results of FIG. 3, IN the cell experiments, METTL-WDR 4-IN-1 showed a significantly reduced inflammatory cytokine expression level at a concentration of 5. Mu.M, and was found to have a better effect.

EXAMPLE 3 therapeutic Effect of METL1 inhibitor METTL-WDR 4-IN-1 on psoriasis

1. Preparation of the medicine:

METTL1-WDR4-IN-1 was dissolved IN DMSO and an external ointment was prepared using a cream base (vaseline) as a carrier to give an ointment (1000-fold concentration screened IN the cell experiment) with a concentration of METTL-WDR 4-IN-1 of 5 mM.

2. Building an animal model:

c57 mice, females, of about 18 grams in weight were selected 6 weeks of age. The ear of the mouse is cleaned, 5% imiquimod ointment is gently smeared on the surface of the ear of the mouse, the dosage is 2 mg/ear/time/day, and the smearing is carried out for 8 days continuously once a day.

3. Drug treatment:

The experimental group, starting on day 1 of the application of imiquimod ointment, was prepared by mixing the drug METTL-WDR 4-IN-1 dissolved IN DMSO IN 2mg of cream base (5 mM ointment drug concentration) at a dose of 2 mg/ear/time/day, once daily. After the medicine is fully absorbed, 5% imiquimod ointment is applied to the ear surface of the mouse lightly, and the dosage is 2 mg/ear/time/day once a day.

The control group is smeared with the same amount of cream matrix, and the dosage and the frequency are the same as before.

The observation index is that the skin state of the ear of the mouse is observed every day, erythema, scales, skin thickness and the like are scored, the scoring standard refers to the PASI scoring standard, and the obtained results are shown in fig. 4, 5 and 6.

As can be seen from analysis of the results of fig. 4, 5 and 6:

according to the results of PASI standards (psoriasis area and severity index), the treatment with METTL-WDR 4-IN-1 can effectively improve psoriasis symptoms, the ear skin of mice can be seen to have reduced erythema, reduced scales, obviously reduced ear thickness, HE staining shows obviously reduced epidermic hyperplasia and inflammatory cell infiltration, qRT-PCR can detect that the relative mRNA expression of downstream inflammatory factors related to psoriasis is obviously reduced after the treatment with the medicament, and further can prove that the METTL-WDR 4-IN-1 medicament has positive therapeutic significance on psoriasis.

EXAMPLE 4 therapeutic Effect of METL1 inhibitor METTL-WDR 4-IN-1 on atopic dermatitis

1. Preparation of the medicine:

METTL1-WDR4-IN-1 was dissolved IN 10% DMSO+90% physiological saline to prepare a drug solution having a concentration of METTL1-WDR4-IN-1 of 5 mM.

2. Building an animal model:

c57 mice, females, of about 18 grams in weight were selected 6 weeks of age. The ear of the mouse was cleaned, and calcipotriol liniment (MC 903, 50. Mu.g/ml) was gently applied to the surface of the ear of the mouse over about 2/3 of the ear at a dose of 2 nmol/ear/time/day for 14 days.

3. Drug treatment:

The experimental group was that 5mM drug METTL-WDR 4-IN-1 dissolved IN 10% DMSO+90% physiological saline was first applied to the ears of mice daily, at a dose of 20. Mu.l/ear/time/day, starting on day 1 of calcipotriol application. After the medicine is fully absorbed, the calcipotriol liniment is gently smeared on the ear surface of the mouse, and the dosage is 2 nmol/ear/time/day once a day.

The control group is smeared with 10% DMSO+90% physiological saline solution with the same amount and the same dosage and the same frequency.

Observations the skin status of the ears of mice were observed daily, and erythema, crusting, etc. were recorded and SCORAD scored.

The results obtained are shown in fig. 7, 8 and 9.

As can be seen from analysis of the results of fig. 7, 8 and 9:

The reduction of dander and erythema IN ears of mice treated with METTL-WDR 4-IN-1, the reduction of SCORAD score (atopic dermatitis score) results show that the SCORAD score is significantly reduced after treatment with METTL-WDR 4-IN-1, HE staining shows that the thickening of epidermis and inflammatory cell infiltration are significantly reduced, qRT-PCR can detect that the relative expression amount of mRNA of inflammatory factors downstream relative to atopic dermatitis is significantly reduced after drug treatment, and the METTL-WDR 4-IN-1 has positive therapeutic significance for atopic dermatitis.

Example 5 siRNA sequences inhibiting METTL Gene expression

The invention also designs an siRNA sequence for inhibiting METTL gene expression. Because the in vivo environment is complex, in order to improve the stability of siRNA, 2-OMe modification is carried out on ribose 2 position of full-strand RNA base, 2-OMe modification is not needed for protecting base at 3 end, and simultaneously, cholesterol modification is carried out on the end of siRNA in order to promote the siRNA to enter cells in vivo, and the cholesterol modification is carried out at 3 end of siRNA sense strand.

Murine sequence 1:

the sense strand of siRNA sequence 1 is CCCACACUUUAAGCGAACGAATT;

The antisense strand of siRNA sequence 1 is UUCGUUCGCUUAAAGUGUGGGTT;

Modified siRNA sequence 1:

Sense strand CCCACACUUUAAGCGAACGAAdTdT;

antisense strand UUCGUUCGCUUAAAGUGUGGGdTdT.

Human sequence 2:

the sense strand of siRNA sequence 2 is GAUGACCCAAAGGAUAAGAAATT;

The antisense strand of siRNA sequence 2 is UUUCUUAUCCUUUGGGUCAUCTT;

the modified siRNA sequence 2 is:

Sense strand GAUGACCCAAAGGAUAAGAAAdTdT;

antisense strand UUUCUUAUCCUUUGGGUCAUCdTdT.

The specific synthesis method adopts a solid-phase phosphoramidite method, wherein the solid-phase carrier is controlled pore glass beads (CPG), the synthesis direction is 3'-5', the sense strand and the antisense strand are synthesized in sequence, and the sense strand and the antisense strand are synthesized separately, ammonolysis, purification and quality inspection, and then annealed in equimolar quantity to become double chains. The solid phase phosphoramidite method synthesizes from the 3 'to 5' end of the oligonucleotide, adding one base per cycle. The positive and negative sense strands are respectively synthesized, and CPG which is already coupled with cholesterol is used as a solid phase carrier, so that after synthesis, 3 ends of the positive and negative sense strands are directly provided with cholesterol modification, namely siRNA sequences with METTL inhibition on expression are synthesized.

The specific synthesis was synthesized by Shaanxi Baiao Spectrum core Biotechnology Co.

Example 6 therapeutic Effect of siRNA sequence 1 inhibiting METTL Gene expression on psoriasis treatment effect verification was performed according to sequence 1 modified in example 5:

Modified SiRNA sequence 1:

sense strand CCCACACUUUAAGCGAACGAAdTdT and antisense strand UUCGUUCGCUUAAAGUGUGGGdTdT.

1. Preparation of the medicine:

METTL1 siRNA was dissolved in sterile ddH ₂ O, and an external ointment was prepared using a cream base (Vaseline) as a carrier, to prepare an ointment with a concentration of METTL siRNA of 0.5 nmol/mg.

2. Building an animal model:

c57 mice, females, of about 18 grams in weight were selected 6 weeks of age. The ear of the mouse is cleaned, 5% imiquimod ointment is gently smeared on the surface of the ear of the mouse, the dosage is 2 mg/ear/time/day, and the smearing is carried out for 8 days continuously once a day.

3. Drug treatment:

the experimental group, starting on day 1 of the imiquimod ointment, was prepared by mixing METTL siRNA in sterile ddH ₂ O into 1mg of cream base (0.5 nmol/mg of ointment) at a dose of 2 mg/ear/time/day once a day. After the medicine is fully absorbed, 5% imiquimod ointment is applied to the ear surface of the mouse lightly, and the dosage is 2 mg/ear/time/day once a day.

The control group is smeared with the same amount of cream matrix, and the dosage and the frequency are the same as before.

The observation index is that the skin state of the ear of the mouse is observed every day, erythema, scales, skin thickness and the like are scored, and the scoring standard refers to the PASI scoring standard. The results obtained are shown in fig. 10, 11, and 12.

As can be seen from analysis of the results of fig. 10, 11 and 12:

According to the results of PASI standards (psoriasis area and severity index), the siRNA sequence drug treatment can effectively improve psoriasis symptoms, the ear skin of a mouse can be seen to have reduced erythema and scales, the ear thickness is obviously reduced, HE staining shows that epidermal hyperplasia and inflammatory cell infiltration are obviously reduced, qRT-PCR can detect that the relative mRNA expression quantity of downstream inflammatory factors related to psoriasis is obviously reduced after drug treatment, and further can prove that the siRNA sequence 1 disclosed by the invention has positive therapeutic significance on psoriasis.

Example 7 therapeutic Effect of siRNA sequence 1 inhibiting METTL Gene expression on atopic dermatitis

Treatment effect verification was performed according to modified sequence 1 of example 5:

Modified siRNA sequence 1:

sense strand CCCACACUUUAAGCGAACGAAdTdT and antisense strand UUCGUUCGCUUAAAGUGUGGGdTdT.

1. Preparation of the medicine:

METTL1 siRNA was dissolved in sterile ddH ₂ O to prepare a drug solution with a concentration of METTL siRNA of 50. Mu. Mol/ml.

2. Building an animal model:

c57 mice, females, of about 18 grams in weight were selected 6 weeks of age. The ear of the mouse was cleaned, and calcipotriol liniment (MC 903, 50. Mu.g/ml) was gently applied to the surface of the ear of the mouse over about 2/3 of the ear at a dose of 2 nmol/ear/time/day for 14 days.

3. Drug treatment:

The experimental group was that 50. Mu. Mol/ml siRNA drug solution in sterile ddH ₂ O water was first applied to the ears of mice daily, at a dose of 20. Mu.l/ear/time/day, starting on day 1 of calcipotriol application. After the medicine is fully absorbed, the calcipotriol liniment is gently smeared on the ear surface of the mouse, and the dosage is 2 nmol/ear/time/day once a day.

The control group is smeared with equal amount of sterile ddH ₂ O water, and the dosage and the frequency are the same as before.

Observations the skin status of the ears of mice were observed daily, and erythema, crusting, etc. were recorded and SCORAD scored. The results obtained are shown in fig. 13, 14 and 15.

As can be seen from analysis of the results of fig. 13, 14 and 15:

The siRNA sequence treated mice had reduced dander at the ear and reduced erythema. According to the SCORAD scoring result, the SCORAD score is obviously reduced after the siRNA sequence treatment, HE staining shows that the epidermis thickening and inflammatory cell infiltration are obviously reduced, and qRT-PCR can detect that the relative mRNA expression quantity of the downstream inflammatory factors related to the atopic dermatitis is obviously reduced after the drug treatment, so that the siRNA sequence 1 has positive therapeutic significance on the atopic dermatitis.

Example 8 therapeutic Effect of siRNA sequence 2 inhibiting METTL Gene expression on psoriasis treatment effect verification was performed according to sequence 2 modified in example 5:

the modified siRNA sequence 2 is:

Sense strand GAUGACCCAAAGGAUAAGAAAdTdT and antisense strand UUUCUUAUCCUUUGGGUCAUCdTdT.

Cell model construction:

taking HaCaT cells in logarithmic growth phase, preparing single cell suspension after digestion, adjusting the cell concentration to 5X 10 ⁴ cells/mL, adding 2mL of cell suspension (1X 10 ⁵ cells/hole) into each hole of a 6-hole plate, slightly horizontally shaking to ensure that the cells are uniformly distributed, and then placing the cells in a 37 ℃ incubator for culturing for 12 hours;

When the cells are adhered to the wall and grow to fuse 30+/-5%, the old culture medium is gently sucked, si-NC and si-METTL1 (shown in figure 16) are added into each hole according to the experimental design, and the culture is continued for 8 hours after the mixture is gently mixed;

After the interference is finished, 10 mul of cytokine M5 (concentration: OSM 10ng/mL, TNF-alpha 10ng/mL, IL-2210ng/mL, IL-17 alpha 10ng/mL, IL-1 alpha 10 ng/mL) is added into the MIX group, and the mixture is gently mixed and then cultured for 24 hours to simulate the psoriasis microenvironment;

After the stimulation of M5 is finished, the culture medium is discarded, the cells are gently washed for 3 times by precooled PBS, 1mL of Trizol is added into each hole to lyse the cells, the lysate is collected after the cells are stood for 15 minutes at room temperature, and the cells are preserved at-80 ℃ or immediately subjected to RNA extraction for analysis of target gene expression change by subsequent qRT-PCR experiments. The results obtained are shown in FIG. 18.

Analysis of the results of FIG. 18 shows that, following intervention of METTL in the HaCaT cell line, the associated downstream inflammatory factors are down-regulated. Proved by the expression of the knockdown METTL, the expression of inflammatory factors of a psoriasis cell model can be obviously reduced, which proves that the siRNA sequence 2 has positive therapeutic significance on psoriasis.

Example 9 therapeutic Effect of siRNA sequence 2 inhibiting METTL Gene expression on psoriasis treatment effect verification was performed according to sequence 2 modified in example 5:

The modified siRNA sequence 2 is a sense strand GAUGACCCAAAGGAUAAGAAAdTdT;

antisense strand UUUCUUAUCCUUUGGGUCAUCdTdT.

Cell model construction:

taking HaCaT cells in logarithmic growth phase, preparing single cell suspension after digestion, adjusting the cell concentration to 5X 10 ⁴ cells/mL, adding 2mL of cell suspension (1X 10 ⁵ cells/hole) into each hole of a 6-hole plate, slightly horizontally shaking to ensure that the cells are uniformly distributed, and then placing the cells in a 37 ℃ incubator for culturing for 12 hours;

When the cells are adhered to the wall and grow to fuse 30+/-5%, the old culture medium is gently sucked, si-NC and si-METTL1 (shown in figure 17) are added into each hole according to the experimental design, and the culture is continued for 8 hours after the mixture is gently mixed;

After the interference is finished, adding 20ng/ml TSLP protein into a TSLP group, and continuously culturing for 24 hours after gentle mixing to simulate the atopic dermatitis microenvironment;

After the TSLP stimulation was completed, the medium was discarded, the cells were gently washed 3 times with pre-chilled PBS, 1mL Trizol was added to each well, the lysate was collected after 15 minutes at room temperature, and the cells were stored at-80℃or immediately subjected to RNA extraction for analysis of target gene expression changes in the subsequent qRT-PCR experiments, and the results were shown in FIG. 19.

Analysis of the results in FIG. 19 shows that the relevant downstream inflammatory factors are down-regulated after intervention of METTL in the HaCaT cell line. Proved by the expression of the knockdown METTL1, the expression of inflammatory factors of an atopic dermatitis cell model can be obviously reduced, which proves that the siRNA sequence 2 has positive therapeutic significance on the atopic dermatitis.

The above embodiments are only for illustrating the technical solution of the present invention and not for limiting the same, and although the present invention has been described in detail with reference to the preferred embodiments, it should be understood by those skilled in the art that modifications and equivalents may be made thereto without departing from the spirit and scope of the technical solution of the present invention, which is intended to be covered by the scope of the claims of the present invention. The technology, shape, and construction parts of the present invention, which are not described in detail, are known in the art.

Claims (10)

1. Use of METTL1 as a target in the development, screening and/or preparation of drugs for the treatment of erythematous and scaly skin diseases. 2. The use according to claim 1, characterized in that the target is used in the development, screening and/or preparation of drugs for treating psoriasis. 3. The use according to claim 1, characterized in that the target is used in the development, screening and/or preparation of drugs for treating atopic dermatitis. 4. Use of METTL1 inhibitors in the preparation of drugs for the treatment of erythematous and scaly skin diseases. 5. The use according to claim 4, characterized in that the METTL1 inhibitor is used in the preparation of a medicament for treating psoriasis. 6 . The use according to claim 4 , wherein the METTL1 inhibitor is used in the preparation of a medicament for treating atopic dermatitis. 7 . The use according to claim 4 , wherein the METTL1 inhibitor is at least one of a monoclonal antibody, a small molecule compound or a nucleic acid inhibitor that specifically inhibits METTL1 activity. 8 . The use according to claim 7 , wherein the METTL1 inhibitor is METTL1-WDR4-IN-1. 9. The use according to claim 7, characterized in that the METTL1 inhibitor is a siRNA sequence, the sequence of which is as follows: siRNA sequence 1: Sense strand: CCCACACUUUAAGCGAACGAATT; Antisense strand: UUCGUUCGCUUAAAGUGUGGGTT; siRNA sequence 2: Sense chain: GAUGACCCAAAGGAUAAGAAATT; antisense chain: UUUCUUAUCCUUUGGGUCAUCTT. 10. The use according to any one of claims 4 to 9, characterized in that the drug further comprises a pharmaceutically acceptable excipient.