Spiroconjugated 1,2,3-triazolo[5,1-b]1,3,4-thiadiazine stimulates functional activity of fibroblasts under skin injury regeneration
Abstract
Background and purpose: One of the most important mechanisms of tissue regeneration is the high functional activity of cells, including proliferation. Currently, there are practically no effective skin cell activators on the pharmaceutical market. The purpose of this work was to demonstrate the stimulating effect of spiroconjugated 1,2,3-triazolo[5,1-b]1,3,4-thiadiazine (STT) on the functional activity of fibroblasts.
Experimental approach: STT containing ointment for dermal application was made. To assess in vivo effect of the STT a linear wound model in rats was tested. A combination of histological techniques and mechanical testing was employed to estimate the stimulating effect of STT on the functional activity of fibroblasts.
Findings/Results: The STT significantly increased the number of fibroblasts as well as the density and order of produced collagen fibers in the dermis during the wound healing process. As a result, a tissue was formed at the site of damage with the structure corresponding to normal skin. In addition, skin functions were restored, in particular mechanically.
Conclusion and implications: The results suggested the stimulating effect of the STT on fibroblast activity and demonstrated its potential for skin regeneration.
Keywords
Full Text:
PDFReferences
Shen Y, Ning J, Zhao L, Liu W, Wang T, Yu J, et al. Matrix remodeling associated 7 proteins promote cutaneous wound healing through vimentin in coordinating fibroblast functions. Inflamm Regen. 2023;43(5):1-11.DOI: 10.1186/s41232-023-00256-8.
Gurtner GC, Werner S, Barrandon Y, Longaker MT. Wound repair and regeneration. Nature. 2008;453(7193):314-321.DOI: 10.1038/nature07039.
Reinke JM, Sorg H. Wound repair and regeneration. Eur Surg Res. 2012;49(1):35-43.DOI: 10.1159/000339613.
Cheng F, Shen Y, Mohanasundaram P, Lindstrom M, Ivaska J, Ny T, et al. Vimentin coordinates fibroblast proliferation and keratinocyte differentiation in wound healing via TGF-beta-Slug signaling. Proc Natl Acad Sci USA. 2016;113(30):4320-4327.DOI: 10.1073/pnas.1519197113.
Petrova IM, Zaitsev DV, Zhdanova AV, Khatsko SL, Vysokova OA, Kalinina TA, et al. The assessment 1,2,3-triazolo- [5,1-b]-1,3,4-thiadiazine derivative influence on restoration of the fibrous skin component during regeneration caused by burn injury. Russ J of Biomech. 2022;26(2):31-41.DOI: 10.15593/RJBiomech/2022.2.03.
Otterco AN, Andrade AL, Brassolatti P, Pinto KNZ, Araujo HSS, Parizotto NA. Photobiomodulation mechanisms in the kinetics of the wound healing process in rats. J Photochem Photobiol B. 2018;183:22-29.DOI: 10.1016/j.jphotobiol.2018.04.010.
Eissa AE, Zaki MM. Saeid S, Abdelsalam M, Ali HM, Moustafa AA, et al. In vitro evaluation of the efficacy of hemodialysate (Solcoseryl®) as a wound healing agent in Nile tilapia (Oreochromis niloticus). Int J Vet Sci. 2013;1(2):57-64.DOI: 10.1016/j.ijvsm.2013.09.003.
Yuan J, Hou Q, Chen D, Zhong L, Dai X, Zhu Z, et al. Chitosan/LiCl composite scaffolds promote skin regeneration in full-thickness loss. Sci China Life Sci. 2020;63(4):552-562.DOI: 10.1007/s11427-018-9389-6.
Nozdrin VI, Belousova TA, Iatskovskii AN. Morphological aspects of dermatotrophic action of methyluracil applied epicutaneously. Morfologiia. 2002;122(5):74-78.PMID: 12530313.
Kalinina TA, Bystrykh OA, Pozdina VA, Glukhareva TV, Ulitko MV, Morzherin YY. Synthesis of spiro derivatives of 1,2,3-triazolo[5,1-b][1,3,4]thiadiazines and biological activity thereof. Chem Heterocycl. 2015;51(6):589-592.DOI: 10.1007/s10593-015-1742-1.
Vysokova OA, Zhdanova AV, Petrova IM, Medvedeva SY, Kalinina TA, Khatsko S, et al. Wound-healing effect of spiroconjugated [1,2,3]triazolo[5,1-b][1,3,4] thiadiazine on a linear skin wound model. Pharm Chem J. 2019;53(6):642-645.DOI: 10.1007/s11094-019-02054-4.
Kalinina TA, Bystrykh OA, Glukhareva TV, Morzherin YY. Transformation of 1,2,3-thiadiazolyl hydrazones as method for preparation of 1,2,3-triazolo[5,1-b][1,3,4]thiadiazines. J Heterocycl Chem. 2015;54(1):137-146.DOI: 10.1002/jhet.2554.
Morales-Burgos A, Loosemore MP, Goldberg LH. Postoperative wound care after dermatologic procedures: a comparison of 2 commonly used petrolatum-based ointments. J Drugs Dermatol. 2013;12(2):163-164.PMID: 23377388.
Fang QQ, Wang XF, Zhao WY, Shi BH, Lou D, Chen CY, et al. Development of a chitosan-vaseline gauze dressing with wound-healing properties in murine models. Am J Trop Med Hyg. 2020;102(2):468-475.DOI: 10.4269/ajtmh.19-0387.
Bai H, Kyu-Cheol N, Wang Z, Cui Y, Liu H, Liu H, et al. Regulation of inflammatory microenvironment using a self-healing hydrogel loaded with BM-MSCs for advanced wound healing in rat diabetic foot ulcers. J Tissue Eng. 2020;11:1-13.DOI: 10.1177/2041731420947242.
Rogel MR, Soni PN, Troken JR, Sitikov A, Trejo HE, Ridge KM. Vimentin is sufficient and required for wound repair and remodeling in alveolar epithelial cells. FASEB J. 2011; 25(11): 3873-3883.DOI: 10.1096/fj.10-170795.
Bleaken BM, Menko AS, Walker JL. Cells activated for wound repair have the potential to direct collective invasion of an epithelium. Mol. Biol. Cell. 2016;27(3):451-465.DOI: 10.1091/mbc.E15-09-0615.
Walker JL, Bleaken BM, Romisher AR, Alnwibit AA, Menko AS. In wound repair vimentin mediates the transition of mesenchymal leader cells to a myofibroblast phenotype. Mol Biol Cell. 2018;29(13):1555-1570.DOI: 10.1091/mbc.E17-06-0364.
Karimi A, Rahmati SM, Navidbakhsh M. Mechanical characterization of the rat and mice skin tissues using histostructural and uniaxial data. Bioengineered, 2015;6(3):153-160.DOI: 10.1080/21655979.2015.1036202.
Chao CYL, Ng GYF, Cheung KK, Zheng YP, Wang LK, Cheing GLY. In vivo and ex vivo approaches to studying the biomechanical properties of healing wounds in rat skin. J Biomech Eng. 2013;135(10):101009,1-8.DOI: 10.1115/1.4025109.
Hudson LG, Newkirk KM, Chandler HL, Choi C, Fossey SL, Parent AE, et al. Cutaneous wound reepithelialization is compromised in mice lacking functional Slug (Snai2). J Dermatol Sci. 2009; 56(1):19-26.DOI: 10.1016/j.jdermsci.2009.06.009.
Boehnke K, Mirancea N, Pavesio A, Fusenig NE, Boukamp P, Stark HJ. Effects of fibroblasts and microenvironment on epidermal regeneration and tissue function in long-term skin equivalents. Eur J Cell Biol. 2007;86(11-12):731-346.DOI: 10.1016/j.ejcb.2006.12.005.
Ivaska J, Pallari HM, Nevo J, Eriksson JE. Novel functions of vimentin in cell adhesion, migration, and signaling. Exp Cell Res. 2007;313(10):2050-2062.DOI: 10.1016/j.yexcr.2007.03.040.
Mendez MG, Kojima SI, Goldman RD. Vimentin induces changes in cell shape, motility, and adhesion during the epithelial to mesenchymal transition. FASEB J. 2010;24(6):1838-1851.DOI: 10.1096/fj.09-151639.
Dave JM, Bayless KJ. Vimentin as an integral regulator of cell adhesion and endothelial sprouting. Microcirculation. 2014;21(4):333-344.DOI: 10.1111/micc.12111.
Battaglia RA, Delic S, Herrmann H, Snider NT. Vimentin on the move: new developments in cell migration. F1000Res. 2018;7:F1000,1-10.DOI: 10.12688/f1000research.15967.1.
Meenakshi J, Jayaraman V, Ramakrishnan KM, Babu M. Keloids and hypertrophic scars: a review. Indian J Plast Surg. 2005;38(2):175-179.DOI: 10.1097/00006534-198911000-00021.
Yang W, Sherman VR, Gludovatz B, Schaible E, Stewart P, Ritchie RO, et al. On the tear resistance of skin. Nat Commun. 2015;6(1): 1-10.DOI: 0.1038/ncomms7649.
Haydont V, Bernard BA, Fortunel NO. Age-related evolutions of the dermis: clinical signs, fibroblast and extracellular matrix dynamics. Mech Ageing Dev. 2019;177:150-156.DOI: 10.1016/j.mad.2018.03.006.
Stunova A, Vistejnova L. Dermal fibroblasts- a heterogeneous population with regulatory function in wound healing. Cytokine Growth Factor Rev. 2018;39:137-150.DOI: 10.1016/j.cytogfr.2018.01.003.
Boink MA, Roffel S, Breetveld M, Thon M, Haasjes MSP, Waaijman T, et al. Comparison of advanced therapy medicinal product gingiva and skin substitutes and their in vitro wound healing potentials. J Tissue Eng Regen Med. 2018;12(2):e1088–e1097.DOI: 10.1002/term.2438.
Refbacks
- There are currently no refbacks.
This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License which allows users to read, copy, distribute and make derivative works for non-commercial purposes from the material, as long as the author of the original work is cited properly.