Targeting Cx43 to Reduce the Severity of Pressure Ulcer Progression
Abstract
:1. Introduction
2. Materials and Methods
2.1. Mice
2.2. Mouse Magnet Double Pinch Ischaemia Reperfusion Model
2.3. Scoring
2.4. Tissue Harvesting and Processing
2.5. Immunofluorescence Staining
2.6. Confocal Imaging
2.7. Quantitative PCR
2.8. Statistics
3. Results
3.1. Double Cycle Pinch Model Results in a Stage 2 Pressure Ulcer
3.2. Histological Analysis of Skin after a Double Pinch (1.5 h(I)/4 h(R)/1.5 h(I)/24 h(R))
3.3. Cytokine and MMP-9 mRNA Expression in a Single Pinch 1.5 h(I)/24 h(R) Compared to a Double Pinch 1.5 h(I)/4 h(R)/1.5 h(I)/24 h(R)
3.4. Cx43asODN Treatment Prevents the Increase of Epidermal Cx43 Protein Levels after 1.5 h(I)/4 h(R)
3.5. Cx43asODN Treatment Prevented Negative Epidermal Changes after 1.5 h(I)/4 h(R)
3.6. Cx43asODN Prevented Epidermal Spongiosis, Loss of Dermal Cells and PC Degradation after 1.5 h(I)/24 h(R)
3.7. Cx43asODN Treatment Reduces Neutrophil Infiltration to the Dermis after 1.5 h(I)/4 h(R)
3.8. HMGB1 Protein Levels Are Significantly Increased after 1.5 h(I)/4 h(R)
3.9. Cx43asODN Treatment Prevents the Increase of HMGB1 Protein Levels after 1.5 h(I)/4 h(R)
3.10. Epidermal RIP3 Protein Levels Increase with I/R Progression after 1.5 h(I)/4 h(R) and 24 h(R)
3.11. Cx43asODN Prevents the Increase of RIP3 Protein Levels during I/R Progression after 1.5 h(I)/4 h(R) and 24 h(R)
3.12. Cx43asODN Treatment Reduces PU Progression and I/R Injury
4. Discussion
4.1. Summary of Key Findings
4.2. Reduction of Cx43 Protein Upregulation and Histological Observations
4.3. Regulating Necroptosis and Preventing PU Progression
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
- Black, J.; Baharestani, M.; Cuddigan, J.; Dorner, B.; Edsberg, L.; Langemo, D.; Posthauer, M.E.; Ratliff, C.; Taler, G.; Panel, N.P.U.A. National Pressure Ulcer Advisory Panel’s updated pressure ulcer staging system. Dermatol. Nurs. 2007, 19, 343–350. [Google Scholar] [CrossRef] [PubMed]
- Edsberg, L.E.; Black, J.M.; Goldberg, M.; McNichol, L.; Moore, L.; Sieggreen, M. Revised National Pressure Ulcer Advisory Panel Pressure Injury Staging System: Revised Pressure Injury Staging System. J. Wound Ostomy Cont. Nurs. 2016, 43, 585–597. [Google Scholar] [CrossRef] [PubMed]
- Mustoe, T. Understanding chronic wounds: A unifying hypothesis on their pathogenesis and implications for therapy. Am. J. Surg. 2004, 187, S65–S70. [Google Scholar] [CrossRef] [PubMed]
- Mustoe, T.A.; O’Shaughnessy, K.; Kloeters, O. Chronic Wound Pathogenesis and Current Treatment Strategies: A Unifying Hypothesis. Plast. Reconstr. Surg. 2006, 117, 35S–41S. [Google Scholar] [CrossRef]
- Al Mutairi, K.B.; Hendrie, D. Global incidence and prevalence of pressure injuries in public hospitals: A systematic review. Wound Med. 2018, 22, 23–31. [Google Scholar] [CrossRef]
- Haesler, E. National Pressure Ulcer Advisory Panel, European Pressure Ulcer Advisory Panel and Pan Pacific Pressure Injury Alliance. In Prevention and Treatment of Pressure Ulcers: Clinical Practice Guideline; Cambridge Media: Osborne Park, Australia, 2014. [Google Scholar]
- Mallah, Z.; Nassar, N.; Badr, L.K. The Effectiveness of a Pressure Ulcer Intervention Program on the Prevalence of Hospital Acquired Pressure Ulcers: Controlled Before and After Study. Appl. Nurs. Res. 2015, 28, 106–113. [Google Scholar] [CrossRef]
- Smith, S.K.; E Ashby, S.; Thomas, L.; Williams, F. Evaluation of a multifactorial approach to reduce the prevalence of pressure injuries in regional Australian acute inpatient care settings. Int. Wound J. 2017, 15, 95–105. [Google Scholar] [CrossRef]
- Atkinson, R.A.; Cullum, N.A. Interventions for pressure ulcers: A summary of evidence for prevention and treatment. Spinal Cord 2018, 56, 186–198. [Google Scholar] [CrossRef]
- Moore, Z.E.H.; Webster, J. Dressings and topical agents for preventing pressure ulcers. Cochrane Database Syst. Rev. 2018, 12. [Google Scholar] [CrossRef]
- Loerakker, S.; Manders, E.; Strijkers, G.J.; Nicolay, K.; Baaijens, F.P.T.; Bader, D.L.; Oomens, C.W.J. The effects of deformation, ischemia, and reperfusion on the development of muscle damage during prolonged loading. J. Appl. Physiol. 2011, 111, 1168–1177. [Google Scholar] [CrossRef]
- Cui, F.-F.; Pan, Y.-Y.; Xie, H.-H.; Wang, X.-H.; Shi, H.-X.; Xiao, J.; Zhang, H.-Y.; Chang, H.-T.; Jiang, L.-P. Pressure Combined with Ischemia/Reperfusion Injury Induces Deep Tissue Injury via Endoplasmic Reticulum Stress in a Rat Pressure Ulcer Model. Int. J. Mol. Sci. 2016, 17, 284. [Google Scholar] [CrossRef] [PubMed]
- Zhou, T.; Prather, E.R.; Garrison, D.E.; Zuo, L. Interplay between ROS and Antioxidants during Ischemia-Reperfusion Injuries in Cardiac and Skeletal Muscle. Int. J. Mol. Sci. 2018, 19, 417. [Google Scholar] [CrossRef] [PubMed]
- Kalogeris, T.; Baines, C.P.; Krenz, M.; Korthuis, R.J. Ischemia/Reperfusion. Compr. Physiol. 2016, 7, 113–170. [Google Scholar] [PubMed]
- Sun, W.; Wu, X.; Gao, H.; Yu, J.; Zhao, W.; Lu, J.J.; Chen, X. Cytosolic calcium mediates RIP1/RIP3 complex-dependent necroptosis through JNK activation and mitochondrial ROS production in human colon cancer cells. Free Radic. Biol. Med. 2017, 108, 433–444. [Google Scholar] [CrossRef] [PubMed]
- Pinton, P.; Giorgi, C.; Siviero, R.; Zecchini, E.; Rizzuto, R. Calcium and apoptosis: ER-mitochondria Ca2+ transfer in the control of apoptosis. Oncogene 2008, 27, 6407–6418. [Google Scholar] [CrossRef] [PubMed]
- Degterev, A.; Huang, Z.; Boyce, M.; Li, Y.; Jagtap, P.; Mizushima, N.; Cuny, G.D.; Mitchison, T.J.; Moskowitz, M.A.; Yuan, J. Chemical inhibitor of nonapoptotic cell death with therapeutic potential for ischemic brain injury. Nat. Chem. Biol. 2005, 1, 112–119. [Google Scholar] [CrossRef] [PubMed]
- Xu, X.; Chua, K.-W.; Chua, C.C.; Liu, C.-F.; Hamdy, R.C.; Chua, B.H. Synergistic protective effects of humanin and necrostatin-1 on hypoxia and ischemia/reperfusion injury. Brain Res. 2010, 1355, 189–194. [Google Scholar] [CrossRef]
- Oerlemans, M.I.F.J.; Liu, J.; Arslan, F.; Ouden, K.; Middelaar, B.J.; Doevendans, P.A.; Sluijter, J.P.G. Inhibition of RIP1-dependent necrosis prevents adverse cardiac remodeling after myocardial ischemia–reperfusion in vivo. Basic Res. Cardiol. 2012, 107, 270. [Google Scholar] [CrossRef]
- Linkermann, A.; Bräsen, J.H.; Himmerkus, N.; Liu, S.; Huber, T.B.; Kunzendorf, U.; Krautwald, S. Rip1 (Receptor-interacting protein kinase 1) mediates necroptosis and contributes to renal ischemia/reperfusion injury. Kidney Int. 2012, 81, 751–761. [Google Scholar] [CrossRef]
- Moriwaki, K.; Chan, F.K.-M. RIP3: A molecular switch for necrosis and inflammation. Minerva Anestesiol. 2013, 27, 1640–1649. [Google Scholar] [CrossRef]
- Cai, Z.; Liu, Z.-G. Execution of RIPK3-regulated necrosis. Mol. Cell. Oncol. 2014, 1, e960759. [Google Scholar] [CrossRef] [PubMed]
- Heckmann, B.L.; Tummers, B.; Green, D.R. Crashing the computer: Apoptosis vs. necroptosis in neuroinflammation. Cell Death Differ. 2018, 26, 41–52. [Google Scholar] [CrossRef] [PubMed]
- Raucci, A.; Palumbo, R.; Bianchi, M.E. HMGB1: A signal of necrosis. Autoimmunity 2007, 40, 285–289. [Google Scholar] [CrossRef] [PubMed]
- Chen, C.-B.; Liu, L.-S.; Zhou, J.; Wang, X.-P.; Han, M.; Jiao, X.-Y.; He, X.-S.; Yuan, X.-P. Up-Regulation of HMGB1 Exacerbates Renal Ischemia-Reperfusion Injury by Stimulating Inflammatory and Immune Responses through the TLR4 Signaling Pathway in Mice. Cell. Physiol. Biochem. 2017, 41, 2447–2460. [Google Scholar] [CrossRef] [PubMed]
- Tsung, A.; Sahai, R.; Tanaka, H.; Nakao, A.; Fink, M.P.; Lotze, M.T.; Yang, H.; Li, J.; Tracey, K.J.; Geller, D.A.; et al. The nuclear factor HMGB1 mediates hepatic injury after murine liver ischemia-reperfusion. J. Exp. Med. 2005, 201, 1135–1143. [Google Scholar] [CrossRef] [PubMed]
- Wang, C.; Jiang, J.; Zhang, X.; Song, L.; Sun, K.; Xu, R. Inhibiting HMGB1 Reduces Cerebral Ischemia Reperfusion Injury in Diabetic Mice. Inflammation 2016, 39, 1862–1870. [Google Scholar] [CrossRef] [PubMed]
- Xu, H.; Yao, Y.; Su, Z.; Yang, Y.; Kao, R.; Martin, C.M.; Rui, T.; Liu, Z.H.; Dai, D.P.; Ding, F.H.; et al. Endogenous HMGB1 contributes to ischemia-reperfusion-induced myocardial apoptosis by potentiating the effect of TNF-α/JNK. Am. J. Physiol. Circ. Physiol. 2011, 300, H913–H921. [Google Scholar] [CrossRef] [PubMed]
- Liu, L.; Jiang, Y.; Steinle, J.J. Inhibition of HMGB1 protects the retina from ischemia-reperfusion, as well as reduces insulin resistance proteins. PLoS ONE 2017, 12, e0178236. [Google Scholar] [CrossRef] [PubMed]
- Yang, Z.; Deng, Y.; Su, D.; Tian, J.; Gao, Y.; He, Z.; Wang, X. TLR4 as receptor for HMGB1-mediated acute lung injury after liver ischemia/reperfusion injury. Lab. Investig. 2013, 93, 792–800. [Google Scholar] [CrossRef]
- Andrassy, M.; Volz, H.C.; Igwe, J.C.; Funke, B.; Eichberger, S.N.; Kaya, Z.; Buss, S.; Autschbach, F.; Pleger, S.T.; Lukic, I.K.; et al. High-Mobility Group Box-1 in Ischemia-Reperfusion Injury of the Heart. Circulation 2008, 117, 3216–3226. [Google Scholar] [CrossRef]
- Wang, H.; Vishnubhakat, J.M.; Bloom, O.; Zhang, M.; Ombrellino, M.; Sama, A.; Tracey, K.J. Proinflammatory cytokines (tumor necrosis factor and interleukin 1) stimulate release of high mobility group protein-1 by pituicytes. Surgery 1999, 126, 389–392. [Google Scholar] [CrossRef] [PubMed]
- Wang, H.; Bloom, O.; Zhang, M.; Vishnubhakat, J.M.; Ombrellino, M.; Che, J.; Frazier, A.; Yang, H.; Ivanova, S.; Borovikova, L.; et al. HMG-1 as a Late Mediator of Endotoxin Lethality in Mice. Science 1999, 285, 248–251. [Google Scholar] [CrossRef] [PubMed]
- Nielsen, M.S.; Goodenough, D.A.; Paul, D.L. Gap junctions. Compr. Physiol. 2012, 2, 1981–2035. [Google Scholar] [PubMed]
- Söhl, G.; Willecke, K. Gap junctions and the connexin protein family. Cardiovasc. Res. 2004, 62, 228–232. [Google Scholar] [CrossRef] [PubMed]
- Martin, P.E.; Evans, W. Incorporation of connexins into plasma membranes and gap junctions. Cardiovasc. Res. 2004, 62, 378–387. [Google Scholar] [CrossRef]
- Chandrasekhar, A.; Bera, A.K. Hemichannels: Permeants and their effect on development, physiology and death. Cell Biochem. Funct. 2012, 30, 89–100. [Google Scholar] [CrossRef]
- Decrock, E.; Vinken, M.; De Vuyst, E.; Krysko, D.V.; D’herde, K.; Vanhaecke, T.; Vandenabeele, P.; Rogiers, V.; Leybaert, L. Connexin-related signaling in cell death: To live or let die? Cell Death Differ. 2009, 16, 524. [Google Scholar] [CrossRef]
- Kar, R.; Batra, N.; Riquelme, M.A.; Jiang, J.X. Biological role of connexin intercellular channels and hemichannels. Arch. Biochem. Biophys. 2012, 524, 2–15. [Google Scholar] [CrossRef]
- Gossman, D.G.; Zhao, H.-B. Hemichannel-mediated inositol 1,4,5-trisphosphate (IP3) release in the cochlea: A novel mechanism of IP3 intercellular signaling. Cell Commun. Adhes. 2008, 15, 305–315. [Google Scholar] [CrossRef]
- Scott, C.A.; Kelsell, D.P. Key functions for gap junctions in skin and hearing. Biochem. J. 2011, 438, 245–254. [Google Scholar] [CrossRef]
- Scott, C.A.; Tattersall, D.; O’Toole, E.A.; Kelsell, D.P. Connexins in epidermal homeostasis and skin disease. Biochim. et Biophys. Acta (BBA) Biomembr. 2012, 1818, 1952–1961. [Google Scholar] [CrossRef] [PubMed]
- Coutinho, P.; Qiu, C.; Frank, S.; Tamber, K.; Becker, D. Dynamic changes in connexin expression correlate with key events in the wound healing process. Cell Biol. Int. 2003, 27, 525–541. [Google Scholar] [CrossRef] [PubMed]
- Sutcliffe, J.; Chin, K.; Thrasivoulou, C.; Serena, T.; O’Neil, S.; Hu, R.; White, A.; Madden, L.; Richards, T.; Phillips, A.; et al. Abnormal connexin expression in human chronic wounds. Br. J. Dermatol. 2015, 173, 1205–1215. [Google Scholar] [CrossRef] [PubMed]
- Wang, C.M.; Lincoln, J.; Cook, J.E.; Becker, D.L. Abnormal Connexin Expression Underlies Delayed Wound Healing in Diabetic Skin. Diabetes 2007, 56, 2809–2817. [Google Scholar] [CrossRef] [PubMed]
- Haupt, C.; Witte, O.W.; Frahm, C. Up-regulation of Connexin43 in the glial scar following photothrombotic ischemic injury. Mol. Cell. Neurosci. 2007, 35, 89–99. [Google Scholar] [CrossRef] [PubMed]
- Nakase, T.; Yoshida, Y.; Nagata, K. Enhanced Connexin 43 immunoreactivity in penumbral areas in the human brain following ischemia. Glia 2006, 54, 369–375. [Google Scholar] [CrossRef] [PubMed]
- Rami, A.; Volkmann, T.; Winckler, J. Effective Reduction of Neuronal Death by Inhibiting Gap Junctional Intercellular Communication in a Rodent Model of Global Transient Cerebral Ischemia. Exp. Neurol. 2001, 170, 297–304. [Google Scholar] [CrossRef] [PubMed]
- Cotrina, M.L.; Kang, J.; Lin, J.H.-C.; Bueno, E.; Hansen, T.W.; He, L.; Liu, Y.; Nedergaard, M. Astrocytic Gap Junctions Remain Open during Ischemic Conditions. J. Neurosci. 1998, 18, 2520–2537. [Google Scholar] [CrossRef]
- Spray, D.C.; Hanstein, R.; Lopez-Quintero, S.V.; Stout, R.F.; Suadicani, S.O.; Thi, M.M. Gap junctions and Bystander effects: Good Samaritans and executioners. Wiley Interdiscip. Rev. Membr. Transp. Signal. 2012, 2, 1–15. [Google Scholar] [CrossRef]
- Lin, J.H.-C.; Weigel, H.; Cotrina, M.L.; Liu, S.; Bueno, E.; Hansen, A.J.; Hansen, T.W.; Goldman, S.; Nedergaard, M. Gap-junction-mediated propagation and amplification of cell injury. Nat. Neurosci. 1998, 1, 494–500. [Google Scholar] [CrossRef]
- Deng, Z.-H.; Liao, J.; Zhang, J.-Y.; Liang, C.; Song, C.-H.; Han, M.; Wang, L.-H.; Xue, H.; Zhang, K.; Zabeau, L.; et al. Inhibition of the Connexin 43 Elevation May be Involved in the Neuroprotective Activity of Leptin Against Brain Ischemic Injury. Cell. Mol. Neurobiol. 2014, 34, 871–879. [Google Scholar] [CrossRef] [PubMed]
- Wang, N.; De Vuyst, E.; Ponsaerts, R.; Boengler, K.; Palacios-Prado, N.; Wauman, J.; Lai, C.P.; De Bock, M.; Decrock, E.; Bol, M.; et al. Selective inhibition of Cx43 hemichannels by Gap19 and its impact on myocardial ischemia/reperfusion injury. Basic Res. Cardiol. 2012, 108, 1–16. [Google Scholar] [CrossRef] [PubMed]
- Stadler, I.; Zhang, R.-Y.; Oskoui, P.; Whittaker, M.B.S.; Lanzafame, R.J. Development of a Simple, Noninvasive, Clinically Relevant Model of Pressure Ulcers in the Mouse. J. Investig. Surg. 2004, 17, 221–227. [Google Scholar] [CrossRef] [PubMed]
- Yager, D.R.; Zhang, L.-Y.; Liang, H.-X.; Diegelmann, R.F.; Cohen, I.K. Wound Fluids from Human Pressure Ulcers Contain Elevated Matrix Metalloproteinase Levels and Activity Compared to Surgical Wound Fluids. J. Investig. Dermatol. 1996, 107, 743–748. [Google Scholar] [CrossRef] [PubMed]
- Wei, C.-J.; Xu, X.; Lo, C.W. CONNEXINS AND CELL SIGNALING IN DEVELOPMENT AND DISEASE. Annu. Rev. Cell Dev. Biol. 2004, 20, 811–838. [Google Scholar] [CrossRef] [PubMed]
- Brandner, J.M.; Houdek, P.; Hüsing, B.; Kaiser, C.; Moll, I. Connexins 26, 30, and 43: Differences Among Spontaneous, Chronic, and Accelerated Human Wound Healing. J. Investig. Dermatol. 2004, 122, 1310–1320. [Google Scholar] [CrossRef] [PubMed]
- Laird, D.W.; Lampe, P.D. Therapeutic strategies targeting connexins. Nat. Rev. Drug Discov. 2018, 17, 905–921. [Google Scholar] [CrossRef]
- Eefting, F.; Rensing, B.; Wigman, J.; Pannekoek, W.J.; Liu, W.M.; Cramer, M.J.; Lips, D.J.; A Doevendans, P. Role of apoptosis in reperfusion injury. Cardiovasc. Res. 2004, 61, 414–426. [Google Scholar] [CrossRef]
- Vanden Berghe, T.; Linkermann, A.; Jouan-Lanhouet, S.; Walczak, H.; Vandenabeele, P. Regulated necrosis: The expanding network of non-apoptotic cell death pathways. Nat. Rev. Mol. Cell Biol. 2014, 15, 135–147. [Google Scholar] [CrossRef]
- Gago-Fuentes, R.; Fernández-Puente, P.; Megias, D.; Carpintero-Fernández, P.; Mateos, J.; Acea, B.; Fonseca, E.; Blanco, F.J.; Mayan, M.D. Proteomic Analysis of Connexin 43 Reveals Novel Interactors Related to Osteoarthritis. Mol. Cell. Proteom. 2015, 14, 1831–1845. [Google Scholar] [CrossRef]
- Sorgen, P.L.; Trease, A.J.; Spagnol, G.; Delmar, M.; Nielsen, M.S. Protein–Protein Interactions with Connexin 43: Regulation and Function. Int. J. Mol. Sci. 2018, 19, 1428. [Google Scholar] [CrossRef] [PubMed]
- Martins-Marques, T.; Anjo, S.I.; Pereira, P.; Manadas, B.; Girão, H. Interacting Network of the Gap Junction (GJ) Protein Connexin43 (Cx43) is Modulated by Ischemia and Reperfusion in the Heart*. Mol. Cell. Proteom. 2015, 14, 3040–3055. [Google Scholar] [CrossRef] [PubMed]
- Solan, J.L.; Lampe, P.D. Connexin43 phosphorylation: Structural changes and biological effects. Biochem. J. 2009, 419, 261–272. [Google Scholar] [CrossRef] [PubMed]
- Vieira, M.; Fernandes, J.; Carreto, L.; Anuncibay-Soto, B.; Santos, M.; Han, J.; Fernández-López, A.; Duarte, C.; Carvalho, A.; Santos, A. Ischemic insults induce necroptotic cell death in hippocampal neurons through the up-regulation of endogenous RIP3. Neurobiol. Dis. 2014, 68, 26–36. [Google Scholar] [CrossRef] [PubMed]
- Chen, X.; Li, W.; Ren, J.; Huang, D.; He, W.-T.; Song, Y.; Yang, C.; Li, W.; Zheng, X.; Chen, P.; et al. Translocation of mixed lineage kinase domain-like protein to plasma membrane leads to necrotic cell death. Cell Res. 2013, 24, 105–121. [Google Scholar] [CrossRef] [PubMed]
- Schubert, A.-L.; Schubert, W.; Spray, D.C.; Lisanti, M.P. Connexin Family Members Target to Lipid Raft Domains and Interact with Caveolin-1. Biochemistry 2002, 41, 5754–5764. [Google Scholar] [CrossRef]
- Li, W.; Bao, G.; Chen, W.; Qiang, X.; Zhu, S.; Wang, S.; He, M.; Ma, G.; Ochani, M.; Al-Abed, Y.; et al. Connexin 43 Hemichannel as a Novel Mediator of Sterile and Infectious Inflammatory Diseases. Sci. Rep. 2018, 8, 1–15. [Google Scholar] [CrossRef]
- Véliz, L.P.; González, F.G.; Duling, B.R.; Sáez, J.C.; Boric, M.P.; Mitrou, N.; Braam, B.; Cupples, W.A.; Toubas, J.; Beck, S.; et al. Functional role of gap junctions in cytokine-induced leukocyte adhesion to endothelium in vivo. Am. J. Physiol. Circ. Physiol. 2008, 295, H1056–H1066. [Google Scholar] [CrossRef]
- Dyce, P.W.; Li, D.; Barr, K.J.; Kidder, G.M. Connexin43 Is Required for the Maintenance of Multipotency in Skin-Derived Stem Cells. Stem Cells Dev. 2014, 23, 1636–1646. [Google Scholar] [CrossRef]
- Kurose, T.; Hashimoto, M.; Ozawa, J.; Kawamata, S. Analysis of Gene Expression in Experimental Pressure Ulcers in the Rat with Special Reference to Inflammatory Cytokines. PLoS ONE 2015, 10, e0132622. [Google Scholar] [CrossRef]
- Jiang, L.; Dai, Y.; Cui, F.; Pan, Y.; Zhang, H.; Xiao, J.; Xiaobing, F.U. Expression of cytokines, growth factors and apoptosis-related signal molecules in chronic pressure ulcer wounds healing. Spinal Cord 2013, 52, 145–151. [Google Scholar] [CrossRef] [PubMed]
- Zhao, X.-L.; Luo, X.; Wang, Z.-X.; Yang, G.-L.; Liu, J.-Z.; Liu, Y.-Q.; Li, M.; Chen, M.; Xia, Y.-M.; Liu, J.-J.; et al. Local blockage of EMMPRIN impedes pressure ulcers healing in a rat model. Int. J. Clin. Exp. Pathol. 2015, 8, 6692–6699. [Google Scholar] [PubMed]
- Rayment, E.; Upton, Z.; Shooter, G. Increased matrix metalloproteinase-9 (MMP-9) activity observed in chronic wound fluid is related to the clinical severity of the ulcer. Br. J. Dermatol. 2008, 158, 951–961. [Google Scholar] [CrossRef] [PubMed]
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Kwek, M.S.Y.; Thangaveloo, M.; Madden, L.E.; Phillips, A.R.J.; Becker, D.L. Targeting Cx43 to Reduce the Severity of Pressure Ulcer Progression. Cells 2023, 12, 2856. https://doi.org/10.3390/cells12242856
Kwek MSY, Thangaveloo M, Madden LE, Phillips ARJ, Becker DL. Targeting Cx43 to Reduce the Severity of Pressure Ulcer Progression. Cells. 2023; 12(24):2856. https://doi.org/10.3390/cells12242856
Chicago/Turabian StyleKwek, Milton Sheng Yi, Moogaambikai Thangaveloo, Leigh E. Madden, Anthony R. J. Phillips, and David L. Becker. 2023. "Targeting Cx43 to Reduce the Severity of Pressure Ulcer Progression" Cells 12, no. 24: 2856. https://doi.org/10.3390/cells12242856