Wound healing properties of the protein kinase A inhibitor and the mechanisms of their development
The regenerative activity of the protein kinase A inhibitor was investigated using externally on the model of the flap skin wound. The pronounced wound healing effects of the protein kinase A inhibitor had been revealed. They are based on the activation of mesenchymal progenitor cells. The development of this phenomenon was associated with the direct influence of the protein kinase A inhibitor on mesenchymal progenitor cells. The most significant stimulation of their growth potential occurred in the context of the impact of growth factors in particular fibroblast growth factor secreted by the stromal cells. Moreover, in situ, there was an increase not only in proliferating activity but also in the intensity of the specialization processes of progenitors. Without cytokines stimulation, the change in the pattern of cellular cAMP-mediated signal does not affect the maturation rate of precursors.
Ahmed A, Boulton S, Shao H, Akimoto M, Natarajan A, Cheng X, Melacini G. Recent advances in EPAC-targeted therapies: A biophysical perspective. Cells 2019; 8: 1462.
Ali N, Rosenblum MD. Regulatory T cells in skin. Immunology 2017; 152: 372-81.
Chen R, Ji G, Wang L, Ren H, Xi L. Activation of ERK1/2 and TNF-α production are regulated by calcium/calmodulin signaling pathway during Penicillium marneffei infection within human macrophages. Microb Pathog. 2016; 93: 95-99.
Cheng X, Ji Z, Tsalkova T, Mei F. Epac and PKA: A tale of two intracellular cAMP receptors. Acta Biochim Biophys Sin (Shanghai). 2008; 40: 651-62.
Dehkordi AN, Babaheydari FM, Chehelgerdi M, Dehkordi SR. Skin tissue engineering: Wound healing based on stem-cell-based therapeutic strategies. Stem Cell Res Ther. 2019; 10: 111.
Dhalla NS, Müller AL. Protein kinases as drug development targets for heart disease therapy. Pharmaceuticals (Basel) 2010; 3: 2111-45.
Drelon C, Berthon A, Sahut-Barnola I, Mathieu M, Dumontet T, Rodriguez S, Batisse-Lignier M, Tabbal H, Tauveron I, Lefrançois-Martinez AM, Pointud JC, Gomez-Sanchez CE, Vainio S, Shan J, Sacco S, Schedl A, Stratakis CA, Martinez A, Val P. PKA inhibits WNT signalling in adrenal cortex zonation and prevents malignant tumour development. Nat Commun. 2016; 7: 12751.
Driskell RR, Lichtenberger BM, Hoste E, Kretzschmar K, Simons BD, Charalambous M, Ferron SR, Herault Y, Pav-lovic G, Ferguson-Smith AC, Watt FM. Distinct fibroblast lineages determine dermal architecture in skin development and repair. Nature 2013; 504: 277-81.
Durandy A, Kracker S. Increased activation of PI3 kinase-δ predisposes to B-cell lymphoma. Blood 2020; 135: 638-43.
Firdous SM, Sautya D. Medicinal plants with wound healing potential. Bangladesh J Pharmacol. 2018; 13: 41-52.
Formoso K, Lezoualc'h F, Mialet-Perez J. Role of EPAC1 signalosomes in Cell Fate: Friends or Foes? Cells 2020; 9: 1954.
Fu X, Liu G, Halim A, Ju Y, Luo Q, Song AG. Mesenchymal stem cell migration and tissue repair. Cells 2019; 8: 784.
Goldberg ED, Dygai AM, Zhdanov VV, Zyuz’kov GN, Gur’-yantseva LA., Pershina OV, Povet`eva TN, Stavrova LA, Khrichkova TYu. Participation of mesenchymal precursor cells in wound healing on skin flap model. Bull Exp Biol Med. 2006; 142: 116-18.
Hankenson KD, Gagne K, Shaughnessy M. Extracellular signaling molecules to promote fracture healing and bone regeneration. Adv Drug Deliv Rev. 2015; 94: 3-12.
James MA, Lu Y, Liu Y, Vikis HG, You M. RGS17, an over-expressed gene in human lung and prostate cancer, induces tumor cell proliferation through the cyclic AMP-PKA-CREB pathway. Cancer Res. 2009; 69: 2108-16.
Jiang W, Xu J. Immune modulation by mesenchymal stem cells. Cell Prolif. 2020; 53: e12712.
Khalin I, Kocherga G. Arginine glutamate improves healing of radiation-induced skin ulcers in guinea pigs. Int J Radiat Biol. 2013; 89: 1108-15.
Khan DA. Hypersensitivity and immunologic reactions to biologics: Opportunities for the allergist. Ann Allergy Asthma Immunol. 2016; 117: 115-20.
Koga Y, Tsurumaki H, Aoki-Saito H, Sato M, Yatomi M, Take-hara K, Hisada T. Roles of cyclic AMP response element binding activation in the ERK1/2 and p38 MAPK signalling pathway in central nervous system, cardiovascular system, osteoclast differentiation and mucin and cytokine production. Int J Mol Sci. 2019; 20: 1346.
Liu N, Zhang X, Li N, Zhou M, Zhang T, Li S, Cai X, Ji P, Lin Y. Tetrahedral framework nucleic acids promote corneal epithelial wound healing in vitro and in vivo. Small 2019; 15: e1901907.
Manning G, Whyte DB, Martinez R, Hunter T, Sudarsanam S. The protein kinase complement of the human genome. Science 2002; 298: 1912-34.
Mavers M, Ruderman EM, Perlman H. Intracellular signal pathways: Potential for therapies. Curr Rheumatol Rep. 2009; 11: 378-85.
Mishra PJ, Banerjee D. Activation and differentiation of mesenchymal Stem Cells. Methods Mol Biol. 2017; 1554: 201-09.
Motegi SI, Ishikawa O. Mesenchymal stem cells: The roles and functions in cutaneous wound healing and tumor growth. J Dermatol Sci. 2017; 86: 83-89.
Mu Y, Lee SW, Gage FH. Signaling in adult neurogenesis. Curr Opin Neurobiol. 2010; 20: 416-23.
Najeeb S, Zafar MS, Khurshid Z, Zohaib S, Almas K. The role of nutrition in periodontal health: An update. Nutrients 2016; 8: 530.
Pereira RF, Bártolo PJ. Traditional therapies for skin wound healing. Adv Wound Care (New Rochelle). 2016; 5: 208-29.
Ötün B, Yücel UM. Wound healing effect of different extracts of Centaurea pterocaula. Bangladesh J Pharmacol. 2019; 14: 9-16.
Öz BE, Ilhan M, Ozbilgin S, Akkol EK, Acikara ÖB, Saltan G, Keles H, Süntar I. Effects of Alchemilla mollis and Alchemilla persica on the wound healing process. Bangladesh J Pharmacol. 2016; 11: 577-84.
Qureshi Z, Khan T, Shah AJ, Wahid F. Solanum incanum extract enhances wound healing and tissue regeneration in burn mice model. Bangladesh J Pharmacol. 2019; 14: 101-06.
Schuller HM. Inhibitory role of G(i)-coupled receptors on cAMP-driven cancers with focus on opioid receptors in lung adenocarcinoma and its stem cells. Vitam Horm. 2019; 111: 299-311.
Shah D, Mital K. The role of trypsin: Chymotrypsin in tissue repair. Adv Ther. 2018; 35: 31-42.
Silva JR, Burger B, Kühl CMC, Candreva T, Dos Anjos MBP, Rodrigues HG. Wound healing and omega-6 fatty acids: From inflammation to repair. Mediators Inflamm. 2018; 2018.
Smith SA, Newby AC, Bond M. Ending restenosis: Inhibition of vascular smooth muscle cell proliferation by cAMP. Cells 2019; 8: 1447.
Wang PH, Huang BS, Horng HC, Yeh CC, Chen YJ. Wound healing. J Chin Med Assoc. 2018; 81: 94-101.
Wang W, Lu KJ, Yu CH, Huang QL, Du YZ. Nano-drug deli-very systems in wound treatment and skin regeneration. J Nanobiotechnol. 2019; 17: 82.
Wiser I, Tamir E, Kaufman H, Keren E, Avshalom S, Klein D, Heller L, Shapira E. A novel recombinant human collagen-based flowable matrix for chronic lower limb wound management: First results of a clinical trial. Wounds 2019; 31: 103-07.
Yang L, Zhang D, Wu H, Xie S, Zhang M, Zhang B, Zhang B, Tang S. Basic fibroblast growth factor influences epidermal homeostasis of living skin equivalents through affecting fibroblast phenotypes and functions. Skin Pharmacol Physiol. 2018; 31: 229-37.
Yang R, Yang S, Zhao J, Hu X, Chen X, Wang J, Xie J, Xiong K. Progress in studies of epidermal stem cells and their appli-cation in skin tissue engineering. Stem Cell Res Ther. 2020; 11: 303.
Zarei F, Soleimaninejad M. Role of growth factors and biomaterials in wound healing. Artif. Cells Nanomed. Biotechnol. 2018; 46: 906-11.
Zyuz’kov GN, Krapivin AV, Nesterova YuV, Povetieva TN, Zhdanov VV, Suslov NI, Fomina TI, Udut EV, Miroshnichenko LA, Simanina EV, Semenov AA, Kravtsova SS, Dygai AM. Mechanisms of regeneratory effects of baikal Aconite diterpene alkaloids. Bull Exp Biol Med. 2012; 153: 847-51.
Zyuz’kov GN, Stavrova LA, Miroshnichenko LA, Polyakova TYu, Simanina EV. Prospects for the use of NF-кb Inhibitors to stimulate the functions of regeneration-competent cells of nerve tissue and neuroregeneration in ethanol-induced neurodegeneration. Biointerface Res Appl Chem. 2021; 11: 8065-74.
Zyuz’kov GN, Suslov NI, Miroshnichenko LA, Simanina EV, Polyakova TYu, Stavrova LA, Zhdanov VV, Minakova MYu, Udut EV, Udut VV. Halogenated (Cl-ion) songorine is a new original agonist of fibroblast growth factor receptors of neuronal-committed progenitors possessing neuroregenerative effect after cerebral ischemia and hypoxia in experi-mental animals. Biointerface Res Appl Chem. 2019b; 9: 4317-26.
Zyuz’kov GN, Zhdanov VV, Danilets MG, Udut EV, Miroshnichenko LA, Ligacheva AA, Simanina EV, Chaikovskii AV, Trofimova ES, Minakova MYu, Udut VV, Dygai AM. Involvement of cAMP- and IKK-2-dependent signal pathways in the growth capacity of mesenchymal progenitor cells under the influence of basic fibroblast growth factor. Bull Exp Biol Med. 2014; 157: 224-27.
Zyuz’kov GN, Zhdanov VV, Udut EV, Miroshnichenko LA, Polyakova TYu, Stavrova LA, Chaikovskii AV, Simanina EV, Minakova MY, Udut VV. Peculiarities of intracellular signal transduction in the regulation of functions of mesenchymal, neural, and hematopoietic progenitor cells. Bull Exp Biol Med. 2019c; 167: 201-06.
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