COMPOSITION FOR PREVENTING OR TREATING FIBROSIS INCLUDING AN INHIBITOR OF CDK17 EXPRESSION OR ACTIVITY

Abstract

The present disclosure relates to a composition for preventing or treating fibrosis including an inhibitor of cyclin-dependent kinase 17 (CDK17) expression or activity. According to the present disclosure, the inhibitor of CDK17 expression or activity significantly reduces collagen production and cell activity and viability in activated hepatic stellate cells (liver fibrosis cell model), renal tubular epithelial cells (renal fibrosis cell model) in which fibrosis is induced by TGF-β treatment, and alveolar epithelial cells (lung fibrosis cell model) in which fibrosis is induced by TGF-β treatment, indicating that the composition of the present disclosure has an excellent effect in preventing or treating fibrosis.

Claims

1. A pharmaceutical composition for preventing or treating fibrosis, comprising an inhibitor of cyclin-dependent kinase 17 (CDK17) expression or activity.

2. The pharmaceutical composition according to claim 1, wherein the inhibitor of cyclin-dependent kinase 17 (CDK17) expression or activity is a CDK17 ribonucleic acid.

3. The pharmaceutical composition according to claim 2, wherein the ribonucleic acid is siRNA.

4. The pharmaceutical composition according to claim 1, wherein the fibrosis occurs in lungs, kidneys, a liver, a heart, a brain, blood vessels, joints, intestines, skin, soft tissues, bone marrow, a penis, a peritoneum, muscles, a spine, testes, ovaries, breasts, a thyroid, tympanic membranes, a pancreas, a gallbladder, a bladder, or a prostate.

5. The pharmaceutical composition according to claim 1, further comprising a pharmaceutically acceptable carrier.

6. A health functional food for preventing or alleviating fibrosis, comprising an inhibitor of cyclin-dependent kinase 17 (CDK17) expression or activity.

7. A method of preventing or treating fibrosis, comprising administering to a subject a therapeutically effective amount of an inhibitor of CDK17 expression or activity, or a composition comprising the inhibitor of CDK17 expression or activity.

8. The method according to claim 7, wherein the inhibitor of cyclin-dependent kinase 17 (CDK17) expression or activity is a CDK17 ribonucleic acid.

9. The method according to claim 8, wherein the ribonucleic acid is siRNA.

10. The method according to claim 7, wherein the fibrosis occurs in lungs, kidneys, a liver, a heart, a brain, blood vessels, joints, intestines, skin, soft tissues, bone marrow, a penis, a peritoneum, muscles, a spine, testes, ovaries, breasts, a thyroid, tympanic membranes, a pancreas, a gallbladder, a bladder, or a prostate.

11. The method according to claim 7, wherein the composition further comprises a pharmaceutically acceptable carrier.

Description

BRIEF DESCRIPTION OF THE DRAWINGS

[0046] The above and other objects, features and other advantages of the present disclosure will be more clearly understood from the following detailed description taken in conjunction with the accompanying drawings, in which:

[0047] FIG. 1 is a graph showing the knockdown efficiency of CDK17 siRNAs in activated human hepatic stellate cells (hTERT-HSCs) as measured by RT-qPCR;

[0048] FIG. 2 is a graph showing a decrease in collagen-encoding hCOL1A1 mRNA levels by CDK17 siRNAs in hTERT-HSCs as measured by RT-qPCR;

[0049] FIG. 3 includes western blotting results showing a decrease in alpha-SMA protein levels by CDK17 siRNAs in hTERT-HSCs;

[0050] FIG. 4 is a graph showing a decrease in the viability of hTERT-HSCs by CDK17 siRNA treatment, and cell viability was evaluated by absorbance measured at 450 nm using a plate reader;

[0051] FIG. 5 is an RT-qPCR result showing the knockdown efficiency of CDK17 siRNAs in human renal tubular epithelial cells (HK-2 cells) in which fibrosis is induced by TGF-β treatment;

[0052] FIG. 6 is an RT-qPCR result showing a decrease in collagen-encoding hCOL1A1 mRNA levels by CDK17 siRNAs in HK-2 cells in which fibrosis is induced by TGF-β treatment;

[0053] FIG. 7 includes western blotting results showing a decrease in alpha-SMA protein levels by CDK17 siRNAs in HK-2 cells in which fibrosis is induced by TGF-β treatment;

[0054] FIG. 8 is a graph showing a decrease in the viability of HK-2 cells, by CDK17 siRNA treatment, in which fibrosis is induced by TGF-β treatment, and cell viability was evaluated by absorbance measured at 450 nm using a plate reader;

[0055] FIG. 9 is a graph showing the knockdown efficiency of CDK17 siRNA in human alveolar epithelial cells (A549 cells) in which fibrosis is induced by TGF-β treatment, as measured by RT-qPCR;

[0056] FIG. 10 is a RT-qPCR result showing a decrease in a collagen-encoding hCOL1A1 mRNA levels by CDK17 siRNAs in A549 cells in which fibrosis is induced by TGF-β treatment;

[0057] FIG. 11 includes western blotting results showing a decrease in alpha-SMA protein levels by CDK17 siRNAs in A549 cells in which fibrosis is induced by TGF-β treatment; and

[0058] FIG. 12 is a graph showing a decrease in the viability of A549 cells, by CDK17 siRNA treatment, in which fibrosis is induced by TGF-β treatment, and cell viability was evaluated by absorbance measured at 450 nm using a plate reader.

DETAILED DESCRIPTION OF THE DISCLOSURE

[0059] The present disclosure will now be described more fully with reference to the accompanying drawings, in which exemplary embodiments of the disclosure are shown. The disclosure may, however, be embodied in many different forms and should not be construed as being limited to the embodiments set forth herein; rather, these embodiments are provided so that this disclosure will be thorough and complete, and will fully convey the concept of the disclosure to those skilled in the art. The present disclosure is defined only by the categories of the claims.

Example 1: Confirmation of the Efficacy of CDK17 Gene Knockdown in Treatment of Liver Fibrosis

[0060] “Activated hepatic stellate cells” are key in liver fibrosis, and main strategies for treating liver fibrosis based on “activated hepatic stellate cells” include 1) decreasing the viability of “activated hepatic stellate cells”, 2) decreasing the proliferation of “activated hepatic stellate cells”, 3) decreasing the activity of “activated hepatic stellate cells” or converting “activated hepatic stellate cells” into “resting hepatic stellate cells”, and 4) inhibiting collagen production by “activated hepatic stellate cells”. Accordingly, based on the possibility of association between a CDK17 gene and the viability and proliferation of hTERT-HSCs, which are “activated hepatic stellate cells”, as a strategy for treating liver fibrosis, it was confirmed whether CDK17 gene knockdown affected the viability, activity, and collagen production of hTERT-HSCs.

[0061] Specifically, experiments were conducted using three CDK17 siRNAs of different nucleotide sequences.

[0062] 1) Construction of CDK17 siRNAs

[0063] Three different siRNAs for a human CDK17 gene [GenBank accession number: NM_001170464.4] were purchased from BIONEER, and nucleotide sequences of each CDK17 siRNA are as follows.

TABLE-US-00001 Human CDK17 siRNA #1: (sense, SEQ ID NO: 1) GUCCUCUUCACAGUGGAGU and (antisense, SEQ ID NO: 2) ACUCCACUGUGAAGAGGAC Human CDK17 siRNA #2: (sense, SEQ ID NO: 3) CUAACAAACUGCUGUUCUU and (antisense, SEQ ID NO: 4) AAGAACAGCAGUUUGUUAG Human CDK17 siRNA #3: (sense, SEQ ID NO: 5) CAGUACACAGGAUCUUUCA and (antisense, SEQ ID NO: 6) UGAAAGAUCCUGUGUACUG

2) Evaluation of CDK17 Gene Knockdown Efficiency of CDK17 siRNAs

[0064] To evaluate the knockdown efficiency of each of three different CDK17 siRNAs, hTERT-HSCs were seeded on each well of a 24-well plate at a cell density of 2.0×10.sup.4 cells/well. After 24 hours, hTERT-HSCs were subjected to mock treatment or transfected with a negative control siRNA (NC) or each CDK17 siRNA at a final concentration of 100 nM. After incubation for 2 days, RT-qPCR was performed to confirm whether each of the three different CDK17 siRNAs effectively reduced the level of CDK17 mRNA (FIG. 1). As a result, it was confirmed that each of the three different CDK17 siRNAs significantly and effectively reduced CDK17 gene expression.

3) Evaluation of hCOL1A1 Expression after CDK17 siRNA-Mediated CDK17 Gene Knockdown

[0065] hTERT-HSCs were seeded on each well of a 24-well plate at a cell density of 2.0×10.sup.4 cells/well. After 24 hours, hTERT-HSCs were subjected to mock treatment or transfected with a negative control siRNA (NC) or each of three different CDK17 siRNAs at a final concentration of 100 nM. After incubation for 2 days, RT-qPCR was performed to confirm whether each of the three different CDK17 siRNAs significantly and effectively reduced the mRNA level of human alpha-1 type I collagen (hCOL1A1) for collagen production (FIG. 2). As a result, CDK17 gene knockdown significantly reduced collagen production of “activated hepatic stellate cells”, indicating that CDK17 gene knockdown is effective in treating liver fibrosis.

[0066] 4) Evaluation of alpha-SMA expression after CDK17 siRNA-mediated CDK17 gene knockdown

[0067] In treatment of liver fibrosis, it is important to inhibit the activity of “activated hepatic stellate cells”. hTERT-HSCs were seeded on each well of a 24-well plate at a cell density of 2.0×10.sup.4 cells/well. After 24 hours, hTERT-HSCs were subjected to mock treatment or transfected with a negative control siRNA (NC) or each of three different CDK17 siRNAs at a final concentration of 100 nM. After incubation for 2 days, western blotting was performed for an alpha-SMA protein indicating the degree of activation of hTERT-HSCs.

[0068] As a result, compared to mock treatment and the negative control siRNA, in the case of each CDK17 siRNA, the level of the alpha-SMA protein as an activity marker was significantly reduced in hTERT-HSCs (FIG. 3). These results show that CDK17 gene knockdown significantly reduces the activity of “activated hepatic stellate cells”, indicating that CDK17 gene knockdown is effective in treating liver fibrosis.

[0069] 5) Evaluation of the viability of hTERT-HSCs after CDK17 siRNA-mediated CDK17 gene knockdown

[0070] Next, to investigate whether CDK17 gene knockdown affected the viability of “activated hepatic stellate cells”, hTERT-HSCs were treated with each of the three different CDK17 siRNAs, and the viability thereof was checked. Specifically, hTERT-HSCs were seeded on each well of a 96-well plate in a cell density of 3.0×10.sup.3 cells/well. After 24 hours, hTERT-HSCs were subjected to mock treatment or transfected with a negative control siRNA (NC) or each CDK17 siRNA at a final concentration of 100 nM. Then, for 5 days, 10 μl of an EZ-Cytox reagent was added to each well at a predetermined time, incubation was performed for 1 hour, and then absorbance was measured at 450 nm using a plate reader.

[0071] As a result, compared to mock treatment and NC, in the case of the three different CDK17 siRNAs, the viability of hTERT-HSCs was significantly reduced (FIG. 4). These results show that CDK17 gene knockdown significantly reduces the viability of “activated hepatic stellate cells”, indicating that CDK17 gene knockdown is effective in treating liver fibrosis. [76]

Example 2: Confirmation of the efficacy of CDK17 gene knockdown in treatment of

[0072] renal fibrosis

[0073] Renal fibrosis is a phenomenon found basically in most chronic kidney diseases, and renal fibrosis occurs when epithelial cells are converted into myofibroblasts by epithelial-mesenchymal transition (EMT) and extracellular matrix is accumulated in tissues. Transforming growth factor beta (TGF-(3) is known as a main factor that causes this process. Based on these facts, main strategies for treating renal fibrosis include 1) reducing the viability of “human renal tubular epithelial cells (HK-2 cells) in which fibrosis is induced by TGF-β treatment”, 2) reducing the proliferation of “HK-2 cells in which fibrosis is induced by TGF-β treatment”, 3) reducing the activity of “HK-2 cells in which fibrosis is induced by TGF-β treatment”, and 4) inhibiting collagen production by “HK-2 cells in which fibrosis is induced by TGF-β treatment”. Accordingly, based on the possibility of association between CDK17 gene and the viability and proliferation of “HK-2 cells in which fibrosis is induced by TGF-β treatment”, as a strategy for treating renal fibrosis, it was confirmed whether CDK17 gene knockdown affected the viability, activity, and collagen production of “HK-2 cells in which fibrosis is induced by TGF-β treatment”. Specifically, experiments were conducted using three CDK17 siRNAs of different nucleotide sequences.

[0074] 1) Construction of CDK17 siRNAs

[0075] Three different siRNAs for human CDK17 gene [GenBank accession number: NM_001170464.41 were purchased from BIONEER, and nucleotide sequences of each CDK17 siRNA are as follows.

TABLE-US-00002 Human CDK17 siRNA #1: (sense, SEQ ID NO: 1) GUCCUCUUCACAGUGGAGU and (antisense, SEQ ID NO: 2) ACUCCACUGUGAAGAGGAC Human CDK17 siRNA #2: (sense, SEQ ID NO: 3) CUAACAAACUGCUGUUCUU and (antisense, SEQ ID NO: 4) AAGAACAGCAGUUUGUUAG Human CDK17 siRNA #3: (sense, SEQ ID NO: 5) CAGUACACAGGAUCUUUCA and (antisense, SEQ ID NO: 6) UGAAAGAUCCUGUGUACUG

[0076] 2) Evaluation of CDK17 gene knockdown efficiency of CDK17 siRNAs

[0077] To evaluate the knockdown efficiency of each of the three different CDK17 siRNAs, HK-2 cells were seeded on each well of a 24-well plate at a cell density of 4.0×10.sup.4 cells/well. After 24 hours, TGF-β was added to each well at a final concentration of 10 ng/ml, and at the same time, HK-2 cells were subjected to mock treatment or transfected with a negative control siRNA (NC) or each CDK17 siRNA at a final concentration of 100 nM. After incubation for 2 days, RT-qPCR was performed to confirm whether each of the three different CDK17 siRNAs effectively reduced the level of CDK17 mRNA (FIG. 5). As a result, it was confirmed that each of the three different CDK17 siRNA significantly and effectively reduced CDK17 gene expression.

[0078] 3) Evaluation of hCOL1A1 expression after CDK17 siRNA-mediated CDK17 gene knockdown

[0079] HK-2 cells were seeded on each well of a 24-well plate at a cell density of 4.0×10.sup.4 cells/well. After 24 hours, TGF-β was added to each well at a final concentration of 10 ng/ml, and at the same time, HK-2 cells were subjected to mock treatment or transfected with a negative control siRNA (NC) or each of the three different CDK17 siRNAs at a final concentration of 100 nM. After incubation for 2 days, RT-qPCR was performed to confirm whether each of the three different CDK17 siRNAs significantly and effectively reduced the mRNA level of human alpha-1 type I collagen (hCOL1A1) for collagen production (FIG. 6). As a result, CDK17 gene knockdown significantly reduced collagen production by “HK-2 cells in which fibrosis is induced by TGF-β treatment”, indicating that CDK17 gene knockdown is effective in treating renal fibrosis.

4) Evaluation of Alpha-SMA Expression after CDK17 siRNA-Mediated CDK17 Gene Knockdown

[0080] In treating renal fibrosis, it is important to inhibit the activity of “HK-2 cells in which fibrosis is induced by TGF-β treatment”. Specifically, HK-2 cells were seeded on each well of a 24-well plate at a cell density of 4.0×10.sup.4 cells/well. After 24 hours, TGF-β was added to each well at a final concentration of 10 ng/ml, and at the same time, HK-2 cells were subjected to mock treatment or transfected with a negative control siRNA (NC) or each of three different CDK17 siRNAs at a final concentration of 100 nM. After incubation for 2 days, western blotting was performed for an alpha-SMA protein indicating the degree of activation of “HK-2 cells in which fibrosis is induced by TGF-β treatment”.

[0081] As a result, compared to mock treatment and the negative control siRNA, in the case of each CDK17 siRNA, the level of the alpha-SMA protein as an activity marker was significantly reduced in “HK-2 cells in which fibrosis was induced by TGF-β treatment” (FIG. 7). These results show that CDK17 gene knockdown significantly reduces the activity of “HK-2 cells in which fibrosis is induced by TGF-β treatment”, indicating that CDK17 gene knockdown is effective in treating renal fibrosis.

5) Evaluation of the Viability of “HK-2 Cells in which Fibrosis is Induced by TGF-r3 Treatment” after CDK17 siRNA-Mediated CDK17 Gene Knockdown

[0082] Next, to investigate whether CDK17 gene knockdown affected the viability of “HK-2 cells in which fibrosis was induced by TGF-β treatment”, “HK-2 cells in which fibrosis was induced by TGF-β treatment” were treated with each of the three different CDK17 siRNAs, and the viability thereof was evaluated. Specifically, HK-2 cells were seeded on each well of a 96-well plate at a cell density of 5.0×10.sup.3 cells/well. After 24 hours, TGF-β was added to each well at a final concentration of 10 ng/ml, and at the same time, HK-2 cells were subjected to mock treatment or transfected with a negative control siRNA (NC) or each CDK17 siRNA at a final concentration of 100 nM. Then, for 5 days, 10 μl of an EZ-Cytox reagent was added to each well at a predetermined time, incubation was performed for 1 hour, and then absorbance was measured at 450 nm using a plate reader.

[0083] As a result, compared to mock treatment and NC, in the case of the three different CDK17 siRNAs, the viability of “HK-2 cells in which fibrosis was induced by TGF-β treatment” was significantly reduced (FIG. 8). These results show that CDK17 gene knockdown significantly reduces the viability of “HK-2 cells in which fibrosis is induced by TGF-β treatment”, indicating that CDK17 gene knockdown is effective in treating renal fibrosis.

Example 3: Confirmation of the Efficacy of CDK17 Gene Knockdown in Treatment of Lung Fibrosis

[0084] Lung fibrosis is a phenomenon found basically in most chronic lung diseases, and lung fibrosis occurs when epithelial cells are converted into myofibroblasts by epithelial-mesenchymal transition (EMT) and extracellular matrix is accumulated in tissues. Transforming growth factor beta (TGF-β) is known as a main factor that causes this process. Based on these facts, main strategies for treating lung fibrosis include 1) reducing the viability of “human alveolar epithelial cells (A549 cells) in which fibrosis is induced by TGF-β treatment”, 2) reducing the proliferation of “A549 cells in which fibrosis is induced by TGF-β treatment”, 3) reducing the activity of “A549 cells in which fibrosis is induced by TGF-β treatment”, and 4) inhibiting collagen production by “A549 cells in which fibrosis is induced by TGF-β treatment”. Based on the possibility of association between CDK17 gene and the viability and proliferation of “A549 cells in which fibrosis was induced by TGF-β treatment”, as a strategy for treating lung fibrosis, it was confirmed whether CDK17 gene knockdown affected the viability, activity, and collagen production of “A549 cells in which fibrosis was induced by TGF-β treatment”. Specifically, experiments were conducted using three CDK17 siRNAs of different nucleotide sequences. [96] 1) Construction of CDK17 siRNAs [97] Three different siRNAs for human CDK17 gene lGenBank accession number: NM_001170464.41 were purchased from BIONEER, and nucleotide sequences of each CDK17 siRNA are as follows.

TABLE-US-00003 Human CDK17 siRNA #1: (sense, SEQ ID NO: 1) GUCCUCUUCACAGUGGAGU and (antisense, SEQ ID NO: 2) ACUCCACUGUGAAGAGGAC Human CDK17 siRNA #2: (sense, SEQ ID NO: 3) CUAACAAACUGCUGUUCUU and (antisense, SEQ ID NO: 4) AAGAACAGCAGUUUGUUAG  Human CDK17 siRNA #3: (sense, SEQ ID NO: 5) CAGUACACAGGAUCUUUCA and (antisense, SEQ ID NO: 6) UGAAAGAUCCUGUGUACUG

2) Evaluation of CDK17 Gene Knockdown Efficiency of CDK17 siRNAs

[0085] To evaluate the knockdown efficiency of each of the three different CDK17 siRNAs, A549 cells were seeded on each well of a 24-well plate at a cell density of 4.0×10.sup.4 cells/well. After 24 hours, TGF-β was added to each well at a final concentration of 10 ng/ml, and at the same time, A549 cells were subjected to mock treatment or transfected with a negative control siRNA (NC) or each CDK17 siRNA at a final concentration of 100 nM. After incubation for 2 days, RT-qPCR was performed to confirm whether each of the three different CDK17 siRNAs effectively reduced the level of CDK17 mRNA (FIG. 9). As a result, each of the three different CDK17 siRNAs significantly and effectively reduced CDK17 gene expression.

3) Evaluation of hCOL1A1 Expression after CDK17 siRNA-Mediated CDK17 Gene Knockdown

[0086] A549 cells were seeded on each well of a 24-well plate at a cell density of 4.0×10.sup.4 cells/well. After 24 hours, TGF-β was added to each well at a final concentration of 10 ng/ml, and at the same time, A549 cells were subjected to mock treatment or transfected with a negative control siRNA (NC) or each of the three different CDK17 siRNAs at a final concentration of 100 nM. After incubation for 2 days, RT-qPCR was performed to confirm whether each of the three different CDK17 siRNAs significantly and effectively reduced the mRNA level of human alpha-1 type I collagen (hCOL1A1) for collagen production (FIG. 10). As a result, CDK17 gene knockdown significantly inhibited collagen production by “A549 cells in which fibrosis was induced by TGF-β treatment”, indicating that CDK17 gene knockdown is effective in treating lung fibrosis.

4) Evaluation of Alpha-SMA Expression after CDK17 siRNA-Mediated CDK17 Gene Knockdown

[0087] In treating lung fibrosis, it is important to inhibit the activity of “A549 cells in which fibrosis is induced by TGF-β treatment”. Specifically, A549 cells were seeded on each well of a 24-well plate at a cell density of 4.0×10.sup.4 cells/well. After 24 hours, TGF-β was added to each well at a final concentration of 10 ng/ml, and at the same time, A549 cells were subjected to mock treatment or transfected with a negative control siRNA (NC) or each of three different CDK17 siRNAs at a final concentration of 100 nM. After incubation for 2 days, western blotting was performed for an alpha-SMA protein indicating the degree of activation of “A549 cells in which fibrosis was induced by TGF-β treatment”.

[0088] As a result, compared to mock treatment and the negative control siRNA, in the case of each CDK17 siRNA, the level of the alpha-SMA protein as an activity marker was significantly reduced in “A549 cells in which fibrosis was induced by TGF-β treatment” (FIG. 11). These results show that CDK17 gene knockdown significantly reduces the activity of “A549 cells in which fibrosis is induced by TGF-β treatment”, indicating that CDK17 gene knockdown is effective in treating lung fibrosis.

5) Evaluation of the viability of “A549 Cells in which Fibrosis is Induced by TGF-r3 Treatment” after CDK17 siRNA-Mediated CDK17 Gene Knockdown

[0089] Next, to investigate whether CDK17 gene knockdown affected the viability of “A549 cells in which fibrosis was induced by TGF-β treatment”, “A549 cells in which fibrosis was induced by TGF-β treatment” were treated with each of the three different CDK17 siRNAs, and the viability thereof was evaluated. Specifically, A549 cells were seeded on each well of a 96-well plate at a cell density of 5.0×10.sup.3 cells/well. After 24 hours, TGF-β was added to each well at a final concentration of 10 ng/ml, and at the same time, A549 cells were subjected to mock treatment or transfected with a negative control siRNA (NC) or each CDK17 siRNA at a final concentration of 100 nM. Then, for 5 days, 10 μl of an EZ-Cytox reagent was added to each well at a predetermined time, incubation was performed for 1 hour, and then absorbance was measured at 450 nm using a plate reader.

[0090] As a result, compared to mock treatment and NC, in the case of each of the three different CDK17 siRNAs, the viability of “A549 cells in which fibrosis was induced by TGF-β treatment” was significantly reduced (FIG. 12). These results show that CDK17 gene knockdown significantly reduces the viability of “A549 cells in which fibrosis is induced by TGF-β treatment”, indicating that CDK17 gene knockdown is effective in treating lung fibrosis.

[0091] In activated human hepatic stellate cells (liver fibrosis cell model), human renal tubular epithelial cells (renal fibrosis cell model) in which fibrosis is induced by TGF-β treatment, and human alveolar epithelial cells (lung fibrosis cell model) in which fibrosis is induced by TGF-r3 treatment, cell activity and viability can be significantly reduced by CDK17 gene knockdown. In addition, in activated human hepatic stellate cells, human renal tubular epithelial cells in which fibrosis is induced by TGF-β treatment, and human alveolar epithelial cells in which fibrosis is induced by TGF-β treatment, collagen production can be significantly reduced by CDK17 gene knockdown. These findings confirm that CDK17 gene knockdown is effective in treatment of fibrosis.

[0092] According to the present disclosure, an inhibitor of CDK17 expression or activity can be used to prevent or treat fibrosis.

[0093] The aforementioned description of the present disclosure is provided by way of example and those skilled in the art will understand that the present disclosure can be easily changed or modified into other specified forms without change or modification of the technical spirit or essential characteristics of the present disclosure. Therefore, it should be understood that the aforementioned examples are only provided by way of example and not provided to limit the present disclosure. It should be understood that the scope of the present disclosure is defined by the following claims and the disclosure is to cover all modifications, equivalents, and alternatives falling within the spirit and scope of the disclosure as defined by the claims.