CN110227148B - Application of CXCL14 recombinant protein in preparation of corneal drugs - Google Patents
Application of CXCL14 recombinant protein in preparation of corneal drugs Download PDFInfo
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- CN110227148B CN110227148B CN201910594314.1A CN201910594314A CN110227148B CN 110227148 B CN110227148 B CN 110227148B CN 201910594314 A CN201910594314 A CN 201910594314A CN 110227148 B CN110227148 B CN 110227148B
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- A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- A61K38/19—Cytokines; Lymphokines; Interferons
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Abstract
The invention relates to an application of CXCL14 recombinant protein in preparing corneal drugs, which can be as follows: the CXCL14 recombinant protein is applied to the preparation of the medicine for promoting the corneal injury repair; or, the application of the CXCL14 recombinant protein in preparing the medicine for maintaining the cornea tissue structure homeostasis; alternatively, the CXCL14 recombinant protein is used for the preparation of a medicament for promoting proliferation and/or migration of corneal epithelial cells. The CXCL14 recombinant protein can be applied to the preparation of a medicine for promoting corneal injury repair, a medicine for maintaining corneal tissue structure homeostasis and a medicine for promoting corneal epithelial cell proliferation and/or migration, and provides a new idea for the preparation of a medicine for promoting corneal injury.
Description
Technical Field
The invention belongs to the technical field of ophthalmic keratopathy and cytobiology, and particularly relates to application of CXCL14 recombinant protein in preparation of corneal drugs.
Background
The cornea is an important component that constitutes the ocular surface barrier and the dioptric system. The cornea is exposed to the external environment and is easily damaged by various external injuries (such as ultraviolet light injury, eye burn and trauma) and pathological injuries (such as infectious keratitis). The incidence of corneal injury is high, and corneal injury repair failure can cause corneal opacity, corneal epithelium keratinization, neovascularization and the like, and can cause corneal blindness seriously. The prognosis of corneal injury is mainly determined by the dynamic balance between the degree of injury and the cornea repair ability after injury, and is a complex pathophysiological process. Although basic research and clinical treatment on corneal injury repair are greatly improved in recent years, more than 800 patients who are blinded due to corneal diseases and poor corneal injury repair all over the world still have the reason that the molecular mechanism of corneal injury repair is not completely elucidated so far, and the disease course development of a plurality of corneal diseases cannot be effectively inhibited and reversed. The mechanism of repairing corneal epithelial injury is a complex process, such as corneal scarring, corneal haze and even corneal ulceration easily caused by poor injury healing or formation of a persistent corneal epithelial defect; and is therefore a key factor in corneal wound healing. In the process of repairing corneal injury, not only is simple wound healing involved, but also a plurality of factors such as cell activity, inflammatory immunity, neurotrophic factors and potential causes related to the cornea in a systemic manner are combined. Therefore, the focus of research on repairing corneal epithelial injuries is shifted to the related research on molecular mechanisms and signal pathways of the corneal epithelial injuries, and more attention is paid to whether proteins and peptides which can be generated by the body can effectively promote the repairing of the corneal epithelial injuries, and the drugs are characterized in that: due to different action mechanisms, the protein drugs can repair injuries, can also play other functions of protecting the corneal surface, simulating tear components, regenerating innervation, inhibiting oxidative stimulation, inhibiting inflammation, regenerating blood vessels and the like, and have low toxicity and higher safety. Deeply exploring a new mechanism for repairing the corneal injury or providing a new idea for formulating a treatment strategy, and having important practical significance; how to find a cytokine which is effective, beneficial and safe and enables the treatment of the corneal injury repair to be more accurate is a hotspot of current research. The CXCL14 recombinant protein is used as a medicine for promoting the corneal injury repair, and has not been reported at home and abroad.
Through searching, no patent publication related to the present patent application has been found.
Disclosure of Invention
The invention aims to overcome the limitation of a mode for treating corneal injury in the prior art, and provides application of CXCL14 recombinant protein in preparation of a corneal medicament, wherein the CXCL14 recombinant protein can be applied to preparation of a medicament for promoting corneal injury repair, a medicament for maintaining corneal tissue structure homeostasis and a medicament for promoting proliferation and/or migration of corneal epithelial cells, so that a new thought is provided for preparation of the corneal medicament.
The technical scheme adopted by the invention for solving the technical problem is as follows:
an application of CXCL14 recombinant protein in preparing corneal medicine.
Moreover, the applications are: the CXCL14 recombinant protein is applied to the preparation of the medicine for promoting the corneal injury repair; or, the application of the CXCL14 recombinant protein in preparing the medicine for maintaining the cornea tissue structure homeostasis; alternatively, the CXCL14 recombinant protein is used for the preparation of a medicament for promoting proliferation and/or migration of corneal epithelial cells.
Moreover, the CXCL14 recombinant protein has the function of promoting the repair of corneal injury.
Furthermore, the corneal epithelial cell line is the human corneal epithelial cell line HCE-2[50, B1].
The CXCL14 recombinant protein is used as an active ingredient for preparing a medicament for repairing corneal injury and maintaining corneal tissue structure homeostasis.
Moreover, the CXCL14 recombinant protein shows high expression in normal and healthy corneal tissues, has the effects of promoting proliferation and migration of corneal epithelial cells and remarkably promoting corneal injury repair.
The CXCL14 recombinant protein is independently prepared or used as an active ingredient for preparing a cornea medicament.
Furthermore, the CXCL14 recombinant protein is used as an active ingredient for preparing a corneal drug as an eye drop.
The invention has the advantages and positive effects that:
1. the invention provides a new method for preparing the medicine for promoting the corneal injury repair and maintaining the normal steady state of the corneal tissue structure.
2. Different from the existing medicines for promoting the corneal injury repair, the CXCL14 gene is highly expressed in normal healthy corneal tissues, the CXCL14 protein is also highly expressed in normal corneal tissues, and the CXCL14 recombinant protein is used as a therapeutic medicine, so that the safety is higher.
3. The invention relates to application of CXCL14 recombinant protein produced by a genetic engineering technology as a novel medicament in the aspects of promoting corneal cell proliferation and further promoting corneal injury repair. The CXCL14 gene is found to remarkably promote the proliferation of corneal epithelial cells; meanwhile, the CXCL14 recombinant protein can be used as a supplement of the body secreted CXCL14 protein to promote the repair of corneal injury.
4. The invention provides a physiological function of a gene CXCL14 with high expression quantity in normal healthy cornea, and provides a new application of the gene CXCL14 as a medicine for promoting cornea injury repair.
Drawings
FIG. 1 is a diagram showing that the overexpression of CXCL14 promotes the proliferation of human corneal epithelial cells in vitro, and the result shows that the overexpression of CXCL14 has a promoting effect on the proliferation of human corneal epithelial cells HCE-2[50 ], B1];
FIG. 2 is a diagram showing the results of in vitro promotion of injury repair by human corneal epithelial cells HCE-2[50, B1] by overexpression of CXCL14 in the present invention;
FIG. 3 is a graph showing the results of in vivo promotion of rat corneal epithelial injury repair with human CXCL14 recombinant protein, which shows that the protein has a significant promoting effect on rat corneal epithelial injury;
fig. 4 is a graph of corneal responses of CXCL14 during healing in a rat corneal injury model in accordance with the present invention.
Detailed Description
The present invention is described in detail below with reference to the following examples, which are intended to be illustrative and not limiting, and should not be construed as limiting the scope of the invention.
The raw materials used in the invention are conventional commercial products unless otherwise specified; the methods used in the present invention are, unless otherwise specified, conventional in the art.
An application of CXCL14 recombinant protein in preparing corneal medicine.
Preferably, the application is: the CXCL14 recombinant protein is applied to the preparation of the medicine for promoting the corneal injury repair; or, the use of CXCL14 recombinant protein in the preparation of a medicament for maintaining corneal tissue structure homeostasis; alternatively, the CXCL14 recombinant protein is used for the preparation of a medicament for promoting proliferation and/or migration of corneal epithelial cells.
Preferably, the CXCL14 recombinant protein has the function of obviously promoting the repair of corneal injury.
Preferably, the corneal epithelial cell line is human corneal epithelial cell line HCE-2[ 2 ], [50 ], [ B1].
Preferably, the CXCL14 recombinant protein is used as an effective component for preparing a medicament for repairing corneal injury and maintaining corneal tissue structure homeostasis.
Preferably, the CXCL14 recombinant protein shows high expression in normal healthy corneal tissues, has the effects of promoting proliferation and migration of corneal epithelial cells and remarkably promoting corneal injury repair.
Preferably, the CXCL14 protein is a secreted protein in vivo and is readily soluble in water. Therefore, the CXCL14 recombinant protein is independently prepared into a medicament or is used as an effective component to prepare a cornea medicament.
Preferably, the CXCL14 recombinant protein is used as an effective component to prepare the corneal drug which is eye drops.
The relevant verification of the invention is as follows:
it should be particularly noted that in the following examples, techniques using animal experiments and the like are well known to those of ordinary skill in the art and can be found in references such as Wakuta M, morishige N, chikama T I, et al, delayed Wound dosage and photoprotective Changes in neurological clinical trial of the porous diagnostic Goto-Kakizaki Rat [ J ]. Investigative opthalmology & Visual Science,2007,48 (2).
In addition, 10880-HNAE human CXCL14 recombinant protein from Sino Biological company can be used in the examples of the present invention.
Example 1 CXCL14 promotes proliferation of human corneal epithelial cells in vitro
The results of the stable transfection and cell clone proliferation experiments of the human corneal epithelial cell line HCE-2[50 ] and B1 which overexpresses CXCL14 and reduces CXCL14 are shown in FIG. 1, and show that the overexpression of CXCL14 promotes the proliferation of human corneal epithelial cells, and the inhibition of the expression of CXCL14 inhibits the proliferation of human corneal epithelial cells.
Example 2 CXCL14 promotes migration of human corneal epithelial cells in vitro
The human corneal epithelial cell line HCE-2[50 ], B1] is selected, and the influence of over-expression of CXCL14 on the migration capacity of corneal epithelial cells is observed through a scratch experiment, the experimental result is shown in figure 2, and the result shows that the over-expression of CXCL14 has the promotion effect on the migration capacity of the human corneal epithelial cells, and further has the obvious promotion effect on the damage repair of the corneal epithelial cells in vitro.
Example 3 in vivo promotion of the CXCL14 recombinant protein in the repair of corneal epithelial injury in rats
About 250 healthy SD rats are selected, the performance is not limited, the SD rats are divided into a group for spot-using CXCL14 recombinant protein and a control group, all corneal epithelium with the diameter of 5mm at the center of the left eye of the rats is scraped, an experimental group is applied with CXCL14 recombinant protein (20 ug/ml) for four times a day for spot-using, and the comparison and the observation are carried out with the blank control group. The experimental results are shown in fig. 3, and the results show that the CXCL14 recombinant protein has a remarkable repairing effect on rat corneal epithelial injury.
Example 4 CXCL14 can reduce corneal tissue reaction and maintain corneal structure homeostasis during rat corneal injury repair
The corneal reaction condition in the healing process of a rat corneal injury model is observed, the corneal edema turbidity condition of the rat cornea of the group over expressing the CXCL14 is obviously lighter than that of the control group in the injury repairing process, the corneal edema turbidity condition of the rat cornea of the group reducing the CXCL14 is obviously heavier than that of the control group in the injury repairing process, and the result is shown in figure 4, and the result shows that the CXCL14 can reduce the tissue reaction in the corneal injury repairing process and maintain the stable structure.
Although the embodiments of the present invention have been disclosed for illustrative purposes, those skilled in the art will appreciate that: various substitutions, changes and modifications are possible without departing from the spirit and scope of the invention and the appended claims, and therefore the scope of the invention is not limited to the disclosure of the embodiments and the accompanying drawings.
Claims (3)
1. The application of CXCL14 recombinant protein in preparing human cornea medicine is as follows: the application of the CXCL14 recombinant protein in preparing a medicine for promoting corneal injury repair or the application of the CXCL14 recombinant protein in preparing a medicine for promoting proliferation and/or migration of corneal epithelial cells;
the CXCL14 recombinant protein has the function of promoting the repair of corneal injury;
the corneal epithelial cell is a human corneal epithelial cell HCE-2[ 2 ], [50, B1];
the CXCL14 recombinant protein is used as an effective component for preparing a medicine for repairing corneal injury;
the CXCL14 recombinant protein shows high expression in normal healthy corneal tissues, has the functions of promoting proliferation and migration of corneal epithelial cells and simultaneously remarkably promoting corneal injury repair.
2. The use of a CXCL14 recombinant protein according to claim 1 for the preparation of a human corneal medicament, characterized in that: the CXCL14 recombinant protein is independently prepared into a medicament, or is used as an effective component to prepare a cornea medicament.
3. The use of CXCL14 recombinant protein according to claim 1 for the preparation of a human corneal drug, characterized in that: the CXCL14 recombinant protein is used as an effective component to prepare the corneal drug which is eye drops.
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| BRPI0621761A2 (en) * | 2006-06-12 | 2011-12-20 | Therakine Ltd | ophthalmic solution and use of a saline solution, and an effective amount of at least one therapeutic agent |
| US20160310572A1 (en) * | 2013-12-02 | 2016-10-27 | Wayne State University | Compositions and methods to diagnose diabetes and/or to treat negative effects of diabetes |
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Non-Patent Citations (2)
| Title |
|---|
| Expression of CXCL12 and CXCL14 during eye development in chick and mouse;Ana F.Ojeda等;《Gene Expression Patterns》;20131231;第13卷(第8期);摘要，结论部分 * |
| Knockdown of CXCL14 disrupts neurovascular patterning during ocular development;Ana F Ojeda等;《Developmental Biology》;20170331;第423卷(第1期);第86页右栏第一段，第89页左栏第2段 * |
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