For Publishers
DiscoveryMetadataPeer reviewHostingPublishing
For Researchers
JoinPublishReviewCollect
Register
Blog
About
Search
Advanced search
My ScienceOpen
Search
For Publishers
For Researchers
Blog
About
8
views
28
references
 Top references
cited by
8
    
0 reviews
 Review
0
comments
 Comment
0
recommends
+1 Recommend
0 collections
    0
    shares
      376
      similar
       All similar
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      KLF4 Promotes Diabetic Chronic Wound Healing by Suppressing Th17 Cell Differentiation in an MDSC-Dependent Manner

      research-article
      Author(s): 1 , 2 , 1 , 1 , 1 ,
      Publication date (Electronic):
      Journal: Journal of Diabetes Research
      Publisher: Hindawi

      Read this article at

      ScienceOpenPublisherPMC
      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Objectives

          Diabetic wound inflammation deficiencies lead to ulcer development and eventual amputation and disability. Our previous research demonstrates that myeloid-derived suppressor cells (MDSCs) accumulate during inflammation and promote chronic wound healing via the regulation of Kruppel-like factor 4 (KLF4). In this study, we aimed to investigate the potential roles of MDSCs and KLF4 in diabetic wound healing.

          Methods

          An ob/ob mouse pressure ulcer (PU) model was used to evaluate the process of wound healing. The expression levels of KLF4 and IL-17A were measured by real-time PCR, and the population of MDSCs and Th17 cells was measured by flow cytometry. The levels of cytokines were determined by an immunosuppression assay.

          Results

          KLF4 deficiency in the diabetic PU model resulted in decreased accumulation of MDSCs, increased expansion of Th17 cells, and significantly delayed wound healing. Conversely, KLF4 activation by APTO-253 accelerated wound healing accompanied by increased MDSC populations and decreased numbers of Th17 cells. MDSCs have been proven to mediate Th17 differentiation via cytokines, and our in vitro data showed that elevated KLF4 expression in MDSCs resulted in reduced Th17 cell numbers and, thus, decreased levels of cytokines indispensable for Th17 differentiation.

          Conclusions

          Our study revealed a previously unreported function of KLF4-regulated MDSCs in diabetic wound healing and identified APTO-253 as a potential agent to improve the healing of pressure ulcers.

          Related collections

          Most cited references28

          • Record: found
          • Abstract: found
          • Article: not found

          Prevalence and Ethnic Pattern of Diabetes and Prediabetes in China in 2013.

          Limin Wang, Pei Gao, Mei Zhang … (2017)
          Previous studies have shown increasing prevalence of diabetes in China, which now has the world's largest diabetes epidemic.
          Article 0 comments Cited 533 times – based on 0 reviews     Review now
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            The IL-17 Family of Cytokines in Health and Disease

            Mandy McGeachy, Daniel Cua, Sarah Gaffen (2019)
            The interleukin 17 (IL-17) family of cytokines contains 6 structurally related cytokines, IL-17A through IL-17F. IL-17A, the prototypical member of this family, just passed the 25 th anniversary of its discovery. While less is known about IL-17B-F, IL-17A (commonly known as IL-17) has received much attention for its pro-inflammatory role in autoimmune disease. Over the past decade, however, it has become clear that the functions of IL-17 are far more nuanced than simply turning on inflammation. Accumulating evidence indicates that IL-17 has important context- and tissue-dependent roles in maintaining health during response to injury, physiological stress and infection. Here, we discuss the functions of the IL-17 family, with a focus on the balance between the pathogenic and protective roles of IL-17 in cancer and autoimmune disease, including results of therapeutic blockade and novel aspects of IL-17 signal transduction regulation. The IL-17 cytokine family is relatively poorly understood, apart from the prototypical, founding member, IL-17A, which has achieved notoriety for its role in autoimmunity. In this review, McGeachy, Cua and Gaffen discuss the pathogenic and protective roles of the IL-17 family in health, inflammation, injury, microbial regulation and cancer.
            Article 0 comments Cited 398 times – based on 0 reviews     Review now
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              Wound healing: an overview of acute, fibrotic and delayed healing.

              Robert F. Diegelmann, Melissa Evans (2004)
              Acute wounds normally heal in a very orderly and efficient manner characterized by four distinct, but overlapping phases: hemostasis, inflammation, proliferation and remodeling. Specific biological markers characterize healing of acute wounds. Likewise, unique biologic markers also characterize pathologic responses resulting in fibrosis and chronic non-healing ulcers. This review describes the major biological processes associated with both normal and pathologic healing. The normal healing response begins the moment the tissue is injured. As the blood components spill into the site of injury, the platelets come into contact with exposed collagen and other elements of the extracellular matrix. This contact triggers the platelets to release clotting factors as well as essential growth factors and cytokines such as platelet-derived growth factor (PDGF) and transforming growth factor beta (TGF-beta). Following hemostasis, the neutrophils then enter the wound site and begin the critical task of phagocytosis to remove foreign materials, bacteria and damaged tissue. As part of this inflammatory phase, the macrophages appear and continue the process of phagocytosis as well as releasing more PDGF and TGF beta. Once the wound site is cleaned out, fibroblasts migrate in to begin the proliferative phase and deposit new extracellular matrix. The new collagen matrix then becomes cross-linked and organized during the final remodeling phase. In order for this efficient and highly controlled repair process to take place, there are numerous cell-signaling events that are required. In pathologic conditions such as non-healing pressure ulcers, this efficient and orderly process is lost and the ulcers are locked into a state of chronic inflammation characterized by abundant neutrophil infiltration with associated reactive oxygen species and destructive enzymes. Healing proceeds only after the inflammation is controlled. On the opposite end of the spectrum, fibrosis is characterized by excessive matrix deposition and reduced remodeling. Often fibrotic lesions are associated with increased densities of mast cells. By understanding the functional relationships of these biological processes of normal compared to abnormal wound healing, hopefully new strategies can be designed to treat the pathological conditions.
              Article 0 comments Cited 357 times – based on 0 reviews     Review now
                Bookmark
                All references

                Author and article information

                Contributors
                Ying Shi:
                ORCID: https://orcid.org/0000-0003-4439-0592
                Journal
                Journal ID (nlm-ta): J Diabetes Res
                Journal ID (iso-abbrev): J Diabetes Res
                Journal ID (publisher-id): JDR
                Title: Journal of Diabetes Research
                Publisher: Hindawi
                ISSN (Print): 2314-6745
                ISSN (Electronic): 2314-6753
                Publication date Collection: 2021
                Publication date (Electronic): 15 September 2021
                Volume: 2021
                Electronic Location Identifier: 7945117
                Affiliations
                1Department of Urology, Wuhan Union Hospital, Tongji Medical College, Huazhong University of Science & Technology, China
                2International Medical Center, University of Tsukuba Affiliated Hospital, Japan
                Author notes

                Academic Editor: Yun-Feng Yang

                Author information
                https://orcid.org/0000-0002-1816-4818
                https://orcid.org/0000-0002-9879-8289
                https://orcid.org/0000-0003-2560-5674
                https://orcid.org/0000-0003-1783-2009
                https://orcid.org/0000-0003-4439-0592
                Article
                DOI: 10.1155/2021/7945117
                PMC ID: 8457977
                PubMed ID: 34568499
                SO-VID: de4a4d61-7b27-490d-9b74-79ebe3cdf181
                Copyright © Copyright © 2021 Xiong Yang et al.
                License:

                This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                Date received : 13 June 2021
                Date revision received : 24 August 2021
                Date accepted : 30 August 2021
                Funding
                Funded by: National Natural Science Foundation of China
                Award ID: 8160080608
                Categories
                Subject: Research Article

                Data availability:

                Comments

                Comment on this article

                scite_

                Similar content376

                See all similar

                Cited by8

                See all cited by

                Most referenced authors306

                See all reference authors