Skip to content
2000
  1. Home
  2. A-Z Publications
  3. Current Molecular Pharmacology
  4. Volume 17, Issue 1
  5. Article
Volume 17, Issue 1
  • ISSN: 1874-4672
  • E-ISSN: 1874-4702
file format pdf download PDF
side by side viewer icon HTML

Abstract

Background

With the increasing risk of infections and other serious complications, the underlying molecular mechanism of wound healing impairment in diabetes deserves attention. Cold shock proteins (CSPs), including CIRP and RBM3 are highly expressed in the skin; however, it is unknown whether CSPs are involved in the wound-healing impairment of diabetic skin.

Objectives

The objective of this study is to investigate the effects of RBM3 on skin wound healing in diabetes.

Methods

experiments, western blot assay was used to test the levels of proteins in HaCaT cells treated with different concentrations of glucose. RBM3 was over-expressed in HaCaT cells using lentivirus particles. Cell viability was analyzed by Cell-Counting Kit-8 assay and colony formation assay. The migration of HaCaT cells at different concentrations of glucose was evaluated by wound healing assay. experiments, the mouse model of diabetes was established by intraperitoneal injection of streptozotocin. Four weeks later, the mice were anesthetized by intraperitoneal injection of pentobarbital sodium for skin tissue collection or wound healing experiments. RBM3 knockout mice were established by removing exons 2–6 using the clustered regularly interspaced short palindromic repeats (CRISPR)-Cas9 technique and then used in skin wound healing experiments with or without diabetic stress.

Results

In this study, the expression of RBM3, rather than CIRP, was altered in the skin of diabetic specimens, and the RBM3’s overexpression accelerated the cell viability and proliferation of HaCaT cells under high glucose conditions. RBM3 deficiency caused delayed wound healing in RBM3 knockout in diabetic conditions. Moreover. RBM3 enhanced the ERK1/2 signaling pathway, and its inhibitor FR180204 blocked the beneficial effect of RBM3 overexpression on skin wound healing in diabetes.

Conclusion

RBM3 activated the ERK1/2 signal to facilitate skin wound healing in diabetes, offering a novel therapeutic target for its treatment.

© 2024 The Author(s). Published by Bentham Science Publisher.
This is an open access article distributed under the terms of the Creative Commons Attribution 4.0 International Public License (CC-BY 4.0), a copy of which is available at: https://creativecommons.org/licenses/by/4.0/legalcode. This license permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Loading

Article metrics loading...

/content/journals/cmp/10.2174/0118761429260980231005105929
2024-01-01
2025-01-23

  • From This Site

    /content/journals/cmp/10.2174/0118761429260980231005105929
    dcterms_title,dcterms_subject,pub_keyword
    -contentType:Contributor -contentType:Concept -contentType:Institution
    10
    5
Loading full text...

Full text loading...

/deliver/fulltext/cmp/17/1/CMP-17-E18761429260980.html?itemId=/content/journals/cmp/10.2174/0118761429260980231005105929&mimeType=html&fmt=ahah

References

  1. OkonkwoU. DiPietroL. Diabetes and wound angiogenesis.Int. J. Mol. Sci.2017187141910.3390/ijms1807141928671607
     [Google Scholar]
  2. PopM.A. AlmquistB.D. Biomaterials: A potential pathway to healing chronic wounds?Exp. Dermatol.201726976076310.1111/exd.1329028094868
     [Google Scholar]
  3. BarmanP.K. KohT.J. Macrophage dysregulation and impaired skin wound healing in diabetes.Front. Cell Dev. Biol.2020852810.3389/fcell.2020.0052832671072
     [Google Scholar]
  4. SpampinatoS.F. CarusoG.I. De PasqualeR. SortinoM.A. MerloS. The treatment of impaired wound healing in diabetes: Looking among old drugs.Pharmaceuticals20201346010.3390/ph1304006032244718
     [Google Scholar]
  5. DengL. DuC. SongP. ChenT. RuiS. ArmstrongD.G. DengW. The role of oxidative stress and antioxidants in diabetic wound healing.Oxid. Med. Cell. Longev.2021202111110.1155/2021/885275933628388
     [Google Scholar]
  6. ZhangJ. WangX. VikashV. YeQ. WuD. LiuY. DongW. ROS and ROS-mediated cellular signaling.Oxid. Med. Cell. Longev.2016201611810.1155/2016/435096526998193
     [Google Scholar]
  7. AtalayM. OksalaN. LappalainenJ. LaaksonenD. SenC. RoyS. Heat shock proteins in diabetes and wound healing.Curr. Protein Pept. Sci.2009101859510.2174/13892030978731520219275675
     [Google Scholar]
  8. ZhongX. WangT. XieY. WangM. ZhangW. DaiL. LaiJ. NieX. HeX. MadhusudhanT. ZengH. WangH. Activated protein C ameliorates diabetic cardiomyopathy via modulating OTUB1/YB-1/MEF2B axis.Front. Cardiovasc. Med.2021875815810.3389/fcvm.2021.75815834778410
     [Google Scholar]
  9. HigashitsujiH. FujitaT. HigashitsujiH. FujitaJ. Mammalian cold-inducible RNA-binding protein facilitates wound healing through activation of AMP-activated protein kinase.Biochem. Biophys. Res. Commun.202053341191119710.1016/j.bbrc.2020.10.00433041006
     [Google Scholar]
  10. IdrovoJ.P. JacobA. YangW.L. WangZ. YenH.T. NicastroJ. CoppaG.F. WangP. A deficiency in cold-inducible RNA-binding protein accelerates the inflammation phase and improves wound healing.Int. J. Mol. Med.201637242342810.3892/ijmm.2016.245126743936
     [Google Scholar]
  11. SurebanS.M. RamalingamS. NatarajanG. MayR. SubramaniamD. BishnupuriK.S. MorrisonA.R. DieckgraefeB.K. BrackettD.J. PostierR.G. HouchenC.W. AnantS. Translation regulatory factor RBM3 is a proto-oncogene that prevents mitotic catastrophe.Oncogene200827334544455610.1038/onc.2008.9718427544
     [Google Scholar]
  12. ChipS. ZelmerA. OgunsholaO.O. Felderhoff-MueserU. NitschC. BührerC. WellmannS. The RNA-binding protein RBM3 is involved in hypothermia induced neuroprotection.Neurobiol. Dis.201143238839610.1016/j.nbd.2011.04.01021527344
     [Google Scholar]
  13. PerettiD. BastideA. RadfordH. VerityN. MolloyC. MartinM.G. MorenoJ.A. SteinertJ.R. SmithT. DinsdaleD. WillisA.E. MallucciG.R. RBM3 mediates structural plasticity and protective effects of cooling in neurodegeneration.Nature2015518753823623910.1038/nature1414225607368
     [Google Scholar]
  14. CuiZ. ZhangJ. BaoG. XuG. SunY. WangL. ChenJ. JinH. LiuJ. YangL. FengG. LiW. Spatiotemporal profile and essential role of RBM3 expression after spinal cord injury in adult rats.J. Mol. Neurosci.201454225226310.1007/s12031‑014‑0282‑y24668366
     [Google Scholar]
  15. ZhuX. ZelmerA. KapfhammerJ.P. WellmannS. Cold-inducible RBM3 inhibits PERK phosphorylation through cooperation with NF90 to protect cells from endoplasmic reticulum stress.FASEB J.201630262463410.1096/fj.15‑27463926472337
     [Google Scholar]
  16. FengJ. PanW. YangX. LongF. ZhouJ. LiaoY. WangM. RBM3 increases cell survival but disrupts tight junction of microvascular endothelial cells in acute lung injury.J. Surg. Res.202126122623510.1016/j.jss.2020.12.04133460967
     [Google Scholar]
  17. ZhuX. BührerC. WellmannS. Cold-inducible proteins CIRP and RBM3, a unique couple with activities far beyond the cold.Cell. Mol. Life Sci.201673203839385910.1007/s00018‑016‑2253‑727147467
     [Google Scholar]
  18. GilbertE.R. FuZ. LiuD. Development of a nongenetic mouse model of type 2 diabetes.Exp. Diabetes Res.2011201111210.1155/2011/41625422164157
     [Google Scholar]
  19. MaP.F. JiangJ. GaoC. ChengP.P. LiJ.L. HuangX. LinY.Y. LiQ. PengY.Z. CaiM.C. ShaoW. ZhuQ. HanS. QinQ. XiaJ.J. QiZ.Q. Immunosuppressive effect of compound K on islet transplantation in an STZ-induced diabetic mouse model.Diabetes201463103458346910.2337/db14‑001224834979
     [Google Scholar]
  20. BaiY. ShiD. LuH. YangK. ZhaoH. LuB. PangZ. Hypoglycemic effects of Tibetan medicine Huidouba in STZ-induced diabetic mice and db/db mice.Chin. Herb. Med.202113220220910.1016/j.chmed.2021.02.00136117512
     [Google Scholar]
  21. FengJ. LiaoY. XuX. YiQ. HeL. TangL. hnRNP A1 promotes keratinocyte cell survival post UVB radiation through PI3K/Akt/mTOR pathway.Exp. Cell Res.2018362239439910.1016/j.yexcr.2017.12.00229229447
     [Google Scholar]
  22. HuangX. ChenY. YiJ. YiP. JiaJ. LiaoY. FengJ. JiangX. Tetracaine hydrochloride induces cell cycle arrest in melanoma by downregulating hnRNPA1.Toxicol. Appl. Pharmacol.202243411581010.1016/j.taap.2021.11581034822839
     [Google Scholar]
  23. PilotteJ. CunninghamB.A. EdelmanG.M. VanderklishP.W. Developmentally regulated expression of the cold-inducible RNA-binding motif protein 3 in euthermic rat brain.Brain Res.20091258122410.1016/j.brainres.2008.12.05019150436
     [Google Scholar]
  24. WilkinsonH.N. HardmanM.J. Senescence in wound repair: Emerging strategies to target chronic healing wounds.Front. Cell Dev. Biol.2020877310.3389/fcell.2020.0077332850866
     [Google Scholar]
  25. WangW. ZhangF. YanX. TanQ. Wnt7a regulates high autophagic and inflammatory response of epidermis in high-glucose environment.Burns202046112112710.1016/j.burns.2019.07.02531852613
     [Google Scholar]
  26. WangD. JiangY. LiZ. XueL. LiX. LiuY. LiC. WangH. The effect of candida albicans on the expression levels of toll-like receptor 2 and interleukin-8 in hacat cells under high- and low-glucose conditions.Indian J. Dermatol.201863320120729937555
     [Google Scholar]
  27. BhattacharyaS. AggarwalR. Pal SinghV. RamachandranS. DattaM. Downregulation of mirnas during delayed wound healing in diabetes: role of dicer.Mol. Med.201521184786010.2119/molmed.2014.0018626602065
     [Google Scholar]
  28. ZhuangR.J. MaJ. ShiX. JuF. MaS.P. WangL. ChengB.F. MaY.W. WangM. LiT. FengZ.W. YangH.J. Cold-inducible protein RBM3 protects UV irradiation-induced apoptosis in neuroblastoma cells by affecting p38 and JNK pathways and Bcl2 family proteins.J. Mol. Neurosci.201763214215110.1007/s12031‑017‑0964‑328831692
     [Google Scholar]
  29. YangH.J. ZhuangR.J. LiY.B. LiT. YuanX. LeiB.B. XieY.F. WangM. Cold-inducible protein RBM3 mediates hypothermic neuroprotection against neurotoxin rotenone via inhibition on MAPK signalling.J. Cell. Mol. Med.201923107010702010.1111/jcmm.1458831436914
     [Google Scholar]
  30. YangH.J. ShiX. JuF. HaoB.N. MaS.P. WangL. ChengB.F. WangM. Cold shock induced protein rbm3 but not mild hypothermia protects human SH-SY5Y neuroblastoma cells from MPP+-induced neurotoxicity.Front. Neurosci.20181229810.3389/fnins.2018.0029829773975
     [Google Scholar]
  31. WellmannS. TrussM. BruderE. TornilloL. ZelmerA. SeegerK. BührerC. The RNA-binding protein RBM3 is required for cell proliferation and protects against serum deprivation-induced cell death.Pediatr. Res.2010671354110.1203/PDR.0b013e3181c1332619770690
     [Google Scholar]
  32. RoskoskiR.Jr ERK1/2 MAP kinases: Structure, function, and regulation.Pharmacol. Res.201266210514310.1016/j.phrs.2012.04.00522569528
     [Google Scholar]
  33. ParkJ. ShinM.S. HwangG. YamabeN. YooJ.E. KangK. KimJ.C. LeeJ. HamJ. LeeH. Beneficial effects of deoxyshikonin on delayed wound healing in diabetic mice.Int. J. Mol. Sci.20181911366010.3390/ijms1911366030463303
     [Google Scholar]
  34. SinagraT. MerloS. SpampinatoS.F. PasqualeR.D. SortinoM.A. High mobility group box 1 contributes to wound healing induced by inhibition of dipeptidylpeptidase 4 in cultured keratinocytes.Front. Pharmacol.2015612610.3389/fphar.2015.0012626136686
     [Google Scholar]
  35. JereS.W. HoureldN.N. AbrahamseH. Role of the PI3K/AKT (mTOR and GSK3β) signalling pathway and photobiomodulation in diabetic wound healing.Cytokine Growth Factor Rev.201950525910.1016/j.cytogfr.2019.03.00130890300
     [Google Scholar]
  36. FerryA.L. VanderklishP.W. Dupont-VersteegdenE.E. Enhanced survival of skeletal muscle myoblasts in response to overexpression of cold shock protein RBM3.Am. J. Physiol. Cell Physiol.20113012C392C40210.1152/ajpcell.00098.201121593448
     [Google Scholar]
  37. ZhaoW. XuD. CaiG. ZhuX. QianM. LiuW. CuiZ. Spatiotemporal pattern of RNA-binding motif protein 3 expression after spinal cord injury in rats.Cell. Mol. Neurobiol.201434449149910.1007/s10571‑014‑0033‑124570111
     [Google Scholar]
  38. ShiH. YaoR. LianS. LiuP. LiuY. YangY.Y. YangH. LiS. Regulating glycolysis, the TLR4 signal pathway and expression of RBM3 in mouse liver in response to acute cold exposure.Stress201922336637610.1080/10253890.2019.156898730821572
     [Google Scholar]
/content/journals/cmp/10.2174/0118761429260980231005105929
Loading
RBM3 Accelerates Wound Healing of Skin in Diabetes through ERK1/2 Signaling
Curr Mol Pharmacol 17, E18761429260980 (2024); https://doi.org/10.2174/0118761429260980231005105929
/content/journals/cmp/10.2174/0118761429260980231005105929
/content/journals/cmp/10.2174/0118761429260980231005105929
Loading

Data & Media loading...


  • Article Type:     Research Article
Keyword(s): Cell migration; Cold shock proteins; Diabetes; ERK1/2; RBM3; Wound healing

Most Cited Most Cited RSS feed

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error
Please enter a valid_number test