{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,19]],"date-time":"2026-06-19T00:02:53Z","timestamp":1781827373603,"version":"3.54.5"},"reference-count":84,"publisher":"MDPI AG","issue":"23","license":[{"start":{"date-parts":[[2024,12,3]],"date-time":"2024-12-03T00:00:00Z","timestamp":1733184000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Faculty of Medicine of the Heinrich-Heine-University D\u00fcsseldorf"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Wound healing as a result of a skin injury involves a series of dynamic physiological processes, leading to wound closure, re-epithelialization, and the remodeling of the extracellular matrix (ECM). The primary scar formed by the new ECM never fully regains the original tissue\u2019s strength or flexibility. Moreover, in some cases, due to dysregulated fibroblast activity, proliferation, and differentiation, the normal scarring can be replaced by pathological fibrotic tissue, leading to hypertrophic scars or keloids. These disorders can cause significant physical impairment and psychological stress and represent significant challenges in medical management in the wound-healing process. The present study aimed to investigate the therapeutic effects of exogenously applied carbon dioxide (CO2) on fibroblast behavior, focusing on viability, proliferation, migration, and differentiation to myofibroblasts. We found that CO2 exposure for up to 60 min did not significantly affect fibroblast viability, apoptosis rate, or proliferation and migration capacities. However, a notable finding was the significant reduction in \u03b1-smooth muscle actin (\u03b1-SMA) protein expression, indicative of myofibroblast differentiation inhibition, following CO2 exposure. This effect was specific to CO2 and concentration as well as time-dependent, with longer exposure durations leading to greater reductions in \u03b1-SMA expression. Furthermore, the inhibition of myofibroblast differentiation correlated with a statistically significantly reduced glycolytic and mitochondrial energy metabolism, and as a result, with a reduced ATP synthesis rate. This very noticeable decrease in cellular energy levels seemed to be specific to CO2 exposure and could not be observed in the control cultures using nitrogen (N2)-saturated solutions, indicating a unique and hypoxia-independent effect of CO2 on fibroblast metabolism. These findings suggest that exogenously applied CO2 may possess fibroblast differentiation-reducing properties by modulating fibroblast\u2019s energy metabolism and could offer new therapeutic options in the prevention of scar and keloid development.<\/jats:p>","DOI":"10.3390\/ijms252313013","type":"journal-article","created":{"date-parts":[[2024,12,3]],"date-time":"2024-12-03T11:48:56Z","timestamp":1733226536000},"page":"13013","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Exposure of Primary Human Skin Fibroblasts to Carbon Dioxide-Containing Solution Significantly Reduces TGF-\u03b2-Induced Myofibroblast Differentiation In Vitro"],"prefix":"10.3390","volume":"25","author":[{"given":"Maxine","family":"Fleckner","sequence":"first","affiliation":[{"name":"Department for Orthopedics and Trauma Surgery, Medical Faculty and University Hospital D\u00fcsseldorf, Heinrich Heine University D\u00fcsseldorf, 40225 Dusseldorf, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Niklas K.","family":"D\u00f6hmen","sequence":"additional","affiliation":[{"name":"Department for Orthopedics and Trauma Surgery, Medical Faculty and University Hospital D\u00fcsseldorf, Heinrich Heine University D\u00fcsseldorf, 40225 Dusseldorf, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katharina","family":"Salz","sequence":"additional","affiliation":[{"name":"Department for Orthopedics and Trauma Surgery, Medical Faculty and University Hospital D\u00fcsseldorf, Heinrich Heine University D\u00fcsseldorf, 40225 Dusseldorf, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Till","family":"Christophers","sequence":"additional","affiliation":[{"name":"Department for Orthopedics and Trauma Surgery, Medical Faculty and University Hospital D\u00fcsseldorf, Heinrich Heine University D\u00fcsseldorf, 40225 Dusseldorf, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joachim","family":"Windolf","sequence":"additional","affiliation":[{"name":"Department for Orthopedics and Trauma Surgery, Medical Faculty and University Hospital D\u00fcsseldorf, Heinrich Heine University D\u00fcsseldorf, 40225 Dusseldorf, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christoph V.","family":"Suschek","sequence":"additional","affiliation":[{"name":"Department for Orthopedics and Trauma Surgery, Medical Faculty and University Hospital D\u00fcsseldorf, Heinrich Heine University D\u00fcsseldorf, 40225 Dusseldorf, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6043-4308","authenticated-orcid":false,"given":"Lisa","family":"Oezel","sequence":"additional","affiliation":[{"name":"Department for Orthopedics and Trauma Surgery, Medical Faculty and University Hospital D\u00fcsseldorf, Heinrich Heine University D\u00fcsseldorf, 40225 Dusseldorf, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,12,3]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"98","DOI":"10.1038\/ncpgasthep0055","article-title":"Mechanisms of disease: Mechanisms of hepatic fibrosis and therapeutic implications","volume":"1","author":"Friedman","year":"2004","journal-title":"Nat. Clin. Pract. Gastroenterol. Hepatol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"349","DOI":"10.1038\/nrm809","article-title":"Myofibroblasts and mechano-regulation of connective tissue remodelling","volume":"3","author":"Tomasek","year":"2002","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1007\/s11926-006-0055-x","article-title":"The role of circulating fibrocytes in fibrosis","volume":"8","author":"Quan","year":"2006","journal-title":"Curr. Rheumatol. Rep."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"365","DOI":"10.1016\/S0363-5023(86)80143-5","article-title":"The cytoskeleton and extracellular matrix of the Dupuytren\u2019s disease \u201cmyofibroblast\u201d: An immunofluorescence study of a nonmuscle cell type","volume":"11","author":"Tomasek","year":"1986","journal-title":"J. Hand Surg. Am."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1161\/01.HYP.0000153321.13792.b9","article-title":"Angiotensin II and the endothelium: Diverse signals and effects","volume":"45","author":"Watanabe","year":"2005","journal-title":"Hypertension"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"565","DOI":"10.1016\/j.redox.2015.09.009","article-title":"Reciprocal regulation of TGF-\u03b2 and reactive oxygen species: A perverse cycle for fibrosis","volume":"6","author":"Liu","year":"2015","journal-title":"Redox Biol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1016\/j.trsl.2017.09.005","article-title":"Reactive oxygen species as signaling molecules in the development of lung fibrosis","volume":"190","author":"Chandel","year":"2017","journal-title":"Transl. Res."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1458","DOI":"10.1038\/nprot.2006.238","article-title":"Analysis of apoptosis by propidium iodide staining and flow cytometry","volume":"1","author":"Riccardi","year":"2006","journal-title":"Nat. Protoc."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"253","DOI":"10.1515\/hsz-2017-0217","article-title":"TGF-\u03b2 requires the activation of canonical and non-canonical signalling pathways to induce skeletal muscle atrophy","volume":"399","author":"Abrigo","year":"2018","journal-title":"Biol. Chem."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1111\/j.1600-0781.2005.00154.x","article-title":"Phototherapy and photochemotherapy of sclerosing skin diseases","volume":"21","author":"Brenner","year":"2005","journal-title":"Photodermatol. Photo"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1017","DOI":"10.1016\/j.jaad.2008.07.042","article-title":"Ultraviolet A phototherapy for sclerotic skin diseases: A systematic review","volume":"59","author":"Kroft","year":"2008","journal-title":"J. Am. Acad. Dermatol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"118","DOI":"10.1016\/j.jphotobiol.2011.02.018","article-title":"Effects of blue light irradiation on human dermal fibroblasts","volume":"103","author":"Oplander","year":"2011","journal-title":"J. Photochem. Photobiol. B Biol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"781","DOI":"10.1001\/jamadermatol.2018.1408","article-title":"Sirolimus Gel Treatment vs Placebo for Facial Angiofibromas in Patients With Tuberous Sclerosis Complex A Randomized Clinical Trial","volume":"154","author":"Ohno","year":"2018","journal-title":"JAMA Dermatol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"840","DOI":"10.1093\/ptj\/52.8.840","article-title":"A review of cryotherapy","volume":"52","author":"Olson","year":"1972","journal-title":"Phys. Ther."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1742","DOI":"10.1016\/j.jcrs.2016.09.018","article-title":"Outcomes and complications of excimer laser surgery in patients with collagen vascular and other immune-mediated inflammatory diseases","volume":"42","author":"Schallhorn","year":"2016","journal-title":"J. Cataract. Refr Surg."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1580","DOI":"10.1097\/PRS.0b013e3182a8070c","article-title":"Update on scar management: Guidelines for treating Asian patients","volume":"132","author":"Kim","year":"2013","journal-title":"Plast. Reconstr. Surg."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"El Ayadi, A., Jay, J.W., and Prasai, A. (2020). Current Approaches Targeting the Wound Healing Phases to Attenuate Fibrosis and Scarring. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21031105"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"360","DOI":"10.3109\/09546634.2013.806768","article-title":"Are corticosteroids effective for prevention of scar formation after second-degree skin burn?","volume":"25","author":"Taheri","year":"2014","journal-title":"J. Dermatol. Treat."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1007\/s00403-019-01972-3","article-title":"The IL-4\/IL-13 axis in skin fibrosis and scarring: Mechanistic concepts and therapeutic targets","volume":"312","author":"Nguyen","year":"2020","journal-title":"Arch. Dermatol. Res."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"tkac036","DOI":"10.1093\/burnst\/tkac036","article-title":"Skin biomechanics: A potential therapeutic intervention target to reduce scarring","volume":"10","author":"Hosseini","year":"2022","journal-title":"Burn. Trauma"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"973","DOI":"10.1016\/j.drudis.2008.08.009","article-title":"New therapeutics for the prevention and reduction of scarring","volume":"13","author":"Occleston","year":"2008","journal-title":"Drug Discov. Today"},{"key":"ref_22","first-page":"316235","article-title":"Curbing Inflammation in Skin Wound Healing: A Review","volume":"2015","author":"Rosique","year":"2015","journal-title":"Int. J. Inflam."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"37067","DOI":"10.1074\/jbc.M111.290056","article-title":"Elevated CO2 Levels Cause Mitochondrial Dysfunction and Impair Cell Proliferation","volume":"286","author":"Vohwinkel","year":"2011","journal-title":"J. Biol. Chem."},{"key":"ref_24","first-page":"223","article-title":"The role of carbon dioxide therapy in the treatment of chronic wounds","volume":"24","author":"Brandi","year":"2010","journal-title":"In Vivo"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"423","DOI":"10.3233\/CH-141898","article-title":"Effect of transcutaneous application of gaseous carbon dioxide on cutaneous microcirculation","volume":"60","author":"Finzgar","year":"2015","journal-title":"Clin. Hemorheol. Microcirc."},{"key":"ref_26","first-page":"22","article-title":"Effects of an artificially carbonated bath on athletic warm-up","volume":"27","author":"Akamine","year":"1998","journal-title":"J. Hum. Ergol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1523","DOI":"10.1161\/01.CIR.0000159329.40098.66","article-title":"Carbon dioxide-rich water bathing enhances collateral blood flow in ischemic hindlimb via mobilization of endothelial progenitor cells and activation of NO-cGMP system","volume":"111","author":"Irie","year":"2005","journal-title":"Circulation"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1007\/s00484-007-0102-y","article-title":"Immersion in CO2-rich water containing NaCl diminishes blood pressure fluctuation in anesthetized rats","volume":"52","author":"Yamamoto","year":"2007","journal-title":"Int. J. Biometeorol."},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Onishi, Y., Kawamoto, T., Ueha, T., Kishimoto, K., Hara, H., Fukase, N., Toda, M., Harada, R., Minoda, M., and Sakai, Y. (2012). Transcutaneous application of carbon dioxide (CO2) induces mitochondrial apoptosis in human malignant fibrous histiocytoma in vivo. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0049189"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1007","DOI":"10.1007\/s00264-017-3417-2","article-title":"Transcutaneous carbon dioxide application accelerates muscle injury repair in rat models","volume":"41","author":"Akahane","year":"2017","journal-title":"Int. Orthop."},{"key":"ref_31","first-page":"65","article-title":"The fibroblast","volume":"5","author":"Pieraggi","year":"1985","journal-title":"Ann. Pathol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"674","DOI":"10.1097\/00042728-200506000-00011","article-title":"Normal cutaneous wound healing: Clinical correlation with cellular and molecular events","volume":"31","author":"Baum","year":"2005","journal-title":"Dermatol. Surg."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"500","DOI":"10.1002\/path.1427","article-title":"The myofibroblast in wound healing and fibrocontractive diseases","volume":"200","author":"Gabbiani","year":"2003","journal-title":"J. Pathol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1016\/S0074-7696(07)57004-X","article-title":"Fibroblast differentiation in wound healing and fibrosis","volume":"257","author":"Darby","year":"2007","journal-title":"Int. Rev. Cytol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1111\/j.1067-1927.2005.130102.x","article-title":"Tissue repair, contraction, and the myofibroblast","volume":"13","author":"Desmouliere","year":"2005","journal-title":"Wound Repair. Regen."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"471","DOI":"10.1006\/cbir.1995.1090","article-title":"Factors influencing myofibroblast differentiation during wound healing and fibrosis","volume":"19","author":"Desmouliere","year":"1995","journal-title":"Cell Biol. Int."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"633","DOI":"10.1097\/01.PRS.0000101530.33096.5B","article-title":"The effect of myofibroblast on contracture of hypertrophic scar","volume":"113","author":"Shin","year":"2004","journal-title":"Plast. Reconstr. Surg."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"526","DOI":"10.1038\/sj.jid.5700613","article-title":"Formation and function of the myofibroblast during tissue repair","volume":"127","author":"Hinz","year":"2007","journal-title":"J. Investig. Dermatol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"79e","DOI":"10.1097\/PRS.0000000000008667","article-title":"The Most Current Algorithms for the Treatment and Prevention of Hypertrophic Scars and Keloids: A 2020 Update of the Algorithms Published 10 Years Ago","volume":"149","author":"Ogawa","year":"2022","journal-title":"Plast. Reconstr. Surg."},{"key":"ref_40","unstructured":"West, J.B. (2012). Respiratory Physiology: The Essentials, Lippincott Williams & Wilkins."},{"key":"ref_41","unstructured":"Ganong, W.F. (2010). Review of Medical Physiology, McGraw-Hill Medical."},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Tadokoro, Y., Takeda, D., Murakami, A., Yatagai, N., Saito, I., Arimoto, S., Kakei, Y., Akashi, M., and Hasegawa, T. (2023). Transcutaneous carbon dioxide application suppresses the expression of cancer-associated fibroblasts markers in oral squamous cell carcinoma xenograft mouse model. PLoS ONE, 18.","DOI":"10.1371\/journal.pone.0290357"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"e12699","DOI":"10.1111\/dth.12699","article-title":"Is carboxytherapy a good alternative method in the removal of various skin defects?","volume":"31","author":"Kolodziejczak","year":"2018","journal-title":"Dermatol. Ther."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1436","DOI":"10.1111\/jocd.15601","article-title":"Role of HIF-1\u03b1 in pathogenic mechanisms of keloids","volume":"22","author":"Qiu","year":"2023","journal-title":"J. Cosmet. Dermatol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1016\/j.jphs.2017.12.004","article-title":"Role of hypoxia-inducible factor-1 in the development of renal fibrosis in mouse obstructed kidney: Special references to HIF-1 dependent gene expression of profibrogenic molecules","volume":"136","author":"Kabei","year":"2018","journal-title":"J. Pharmacol. Sci."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"C935","DOI":"10.1152\/ajpcell.00458.2023","article-title":"HIF-1 contributes to autophagy activation via BNIP3 to facilitate renal fibrosis in hypoxia in vitro and UUO in vivo","volume":"326","author":"Liu","year":"2024","journal-title":"Am. J. Physiol. Cell Physiol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"390","DOI":"10.1165\/rcmb.2020-0492OC","article-title":"Hepatocyte HIF-1 and Intermittent Hypoxia Independently Impact Liver Fibrosis in Murine Nonalcoholic Fatty Liver Disease","volume":"65","author":"Mesarwi","year":"2021","journal-title":"Am. J. Respir. Cell Mol. Biol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1080\/08941939.2016.1183734","article-title":"HIF-1\u03b1 as a Key Factor in Bile Duct Ligation-Induced Liver Fibrosis in Rats","volume":"30","author":"Moczydlowska","year":"2017","journal-title":"J. Investig. Surg."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"E7091","DOI":"10.1073\/pnas.1721443115","article-title":"Scleral hypoxia is a target for myopia control","volume":"115","author":"Wu","year":"2018","journal-title":"Proc. Natl. Acad. Sci.USA"},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Xu, X., Li, Y., Niu, Z., Xia, J., Dai, K., Wang, C., Yao, W., Guo, Y., Deng, X., and He, J. (2022). Inhibition of HIF-1\u03b1 Attenuates Silica-Induced Pulmonary Fibrosis. J. Environ. Res. Public Health, 19.","DOI":"10.3390\/ijerph19116775"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"390","DOI":"10.1089\/wound.2013.0520","article-title":"The Role of Hypoxia-Inducible Factor in Wound Healing","volume":"3","author":"Hong","year":"2014","journal-title":"Adv. Wound Care"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"3239","DOI":"10.1080\/15384101.2019.1670508","article-title":"HIF-1\u03b1 promotes the keloid development through the activation of TGF-\u03b2\/Smad and TLR4\/MyD88\/NF-\u03baB pathways","volume":"18","author":"Lei","year":"2019","journal-title":"Cell Cycle"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"2157","DOI":"10.1016\/j.jid.2020.01.036","article-title":"Hypoxia and HIF-1\u03b1 Regulate Collagen Production in Keloids","volume":"140","author":"Kang","year":"2020","journal-title":"J. Investig. Dermatol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"e32","DOI":"10.1111\/ajd.12340","article-title":"2ME2 increase radiation-induced apoptosis of keloid fibroblasts by targeting HIF-1\u03b1 in vitro","volume":"57","author":"Long","year":"2016","journal-title":"Australas. J. Dermatol."},{"key":"ref_55","first-page":"E10","article-title":"Role of Hypoxia Inducible Factor-1 Alpha (HIF-1\u03b1) in Cytoglobin Expression and Fibroblast Proliferation of Keloids","volume":"65","author":"Jusman","year":"2019","journal-title":"Kobe J. Med. Sci."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"14026","DOI":"10.1111\/jcmm.16013","article-title":"Metabolic reprogramming of glycolysis and glutamine metabolism are key events in myofibroblast transition in systemic sclerosis pathogenesis","volume":"24","author":"Henderson","year":"2020","journal-title":"J. Cell Mol. Med."},{"key":"ref_57","doi-asserted-by":"crossref","unstructured":"Hewitson, T.D., and Smith, E.R. (2021). A Metabolic Reprogramming of Glycolysis and Glutamine Metabolism Is a Requisite for Renal Fibrogenesis-Why and How?. Front. Physiol., 12.","DOI":"10.3389\/fphys.2021.645857"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"427","DOI":"10.1161\/CIRCRESAHA.120.316958","article-title":"Myofibroblasts and Fibrosis: Mitochondrial and Metabolic Control of Cellular Differentiation","volume":"127","author":"Gibb","year":"2020","journal-title":"Circ. Res."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"25427","DOI":"10.1074\/jbc.M115.646984","article-title":"Metabolic Reprogramming Is Required for Myofibroblast Contractility and Differentiation","volume":"290","author":"Bernard","year":"2015","journal-title":"J. Biol. Chem."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"1029","DOI":"10.1126\/science.1160809","article-title":"Understanding the Warburg effect: The metabolic requirements of cell proliferation","volume":"324","author":"Cantley","year":"2009","journal-title":"Science"},{"key":"ref_61","first-page":"405","article-title":"Increased activity of four glycolytic enzymes in cultured fibroblasts from cystic fibrosis patients","volume":"51","author":"Bardon","year":"1986","journal-title":"Res. Commun. Chem. Pathol. Pharmacol."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"F561","DOI":"10.1152\/ajprenal.00036.2017","article-title":"Inhibiting aerobic glycolysis suppresses renal interstitial fibroblast activation and renal fibrosis","volume":"313","author":"Ding","year":"2017","journal-title":"Am. J. Physiol. Renal Physiol."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"1319","DOI":"10.1053\/j.gastro.2012.07.115","article-title":"Hedgehog controls hepatic stellate cell fate by regulating metabolism","volume":"143","author":"Chen","year":"2012","journal-title":"Gastroenterology"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"740","DOI":"10.1164\/rccm.201201-0084OC","article-title":"Lactic acid is elevated in idiopathic pulmonary fibrosis and induces myofibroblast differentiation via pH-dependent activation of transforming growth factor-\u03b2","volume":"186","author":"Kottmann","year":"2012","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"1462","DOI":"10.1164\/rccm.201504-0780OC","article-title":"Glycolytic Reprogramming in Myofibroblast Differentiation and Lung Fibrosis","volume":"192","author":"Xie","year":"2015","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"216","DOI":"10.1165\/rcmb.2016-0186OC","article-title":"Targeting Hypoxia-Inducible Factor-1\u03b1\/Pyruvate Dehydrogenase Kinase 1 Axis by Dichloroacetate Suppresses Bleomycin-induced Pulmonary Fibrosis","volume":"58","author":"Goodwin","year":"2018","journal-title":"Am. J. Respir. Cell Mol. Biol."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"17807","DOI":"10.1073\/pnas.0803090105","article-title":"A catabolic block does not sufficiently explain how 2-deoxy-D-glucose inhibits cell growth","volume":"105","author":"Ralser","year":"2008","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"1383","DOI":"10.1089\/ars.2007.1714","article-title":"Differential toxic mechanisms of 2-deoxy-D-glucose versus 2-fluorodeoxy-D-glucose in hypoxic and normoxic tumor cells","volume":"9","author":"Kurtoglu","year":"2007","journal-title":"Antioxid. Redox Signal"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"221","DOI":"10.2220\/biomedres.34.221","article-title":"Impact of 2-deoxy-D-glucose on the target metabolome profile of a human endometrial cancer cell line","volume":"34","author":"Urakami","year":"2013","journal-title":"Biomed. Res."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"4996","DOI":"10.1038\/onc.2012.13","article-title":"Switching from aerobic glycolysis to oxidative phosphorylation modulates the sensitivity of mantle cell lymphoma cells to TRAIL","volume":"31","author":"Robinson","year":"2012","journal-title":"Oncogene"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"E337","DOI":"10.1002\/ijc.26420","article-title":"Differential effects of the glycolysis inhibitor 2-deoxy-D-glucose on the activity of pro-apoptotic agents in metastatic melanoma cells, and induction of a cytoprotective autophagic response","volume":"131","author":"Giammarioli","year":"2012","journal-title":"Int. J. Cancer"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"976","DOI":"10.1038\/bjc.2013.391","article-title":"Targeting tumour energy metabolism potentiates the cytotoxicity of 5-aminolevulinic acid photodynamic therapy","volume":"109","author":"Golding","year":"2013","journal-title":"Br. J. Cancer"},{"key":"ref_73","doi-asserted-by":"crossref","unstructured":"Hegmann, L., Sturm, S., Niegisch, G., Windolf, J., and Suschek, C.V. (2022). Enhancement of human bladder carcinoma cell chemosensitivity to Mitomycin C through quasi-monochromatic blue light (\u03bb = 453 \u00b1 10 nm). J. Photochem. Photobiol. B Biol., 236.","DOI":"10.1016\/j.jphotobiol.2022.112582"},{"key":"ref_74","doi-asserted-by":"crossref","unstructured":"Sturm, S., Niegisch, G., Windolf, J., and Suschek, C.V. (2024). Exposure of Bladder Cancer Cells to Blue Light (\u03bb = 453 nm) in the Presence of Riboflavin Synergistically Enhances the Cytotoxic Efficiency of Gemcitabine. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms25094868"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"826","DOI":"10.1097\/PRS.0b013e318199ef31","article-title":"Content of the growth factors bFGF, IGF-1, VEGF, and PDGF-BB in freshly harvested lipoaspirate after centrifugation and incubation","volume":"123","author":"Pallua","year":"2009","journal-title":"Plast. Reconstr. Surg."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1016\/j.niox.2012.09.003","article-title":"Characterization of novel nitrite-based nitric oxide generating delivery systems for topical dermal application","volume":"28","author":"Oplander","year":"2013","journal-title":"Nitric Oxide Biol. Chem."},{"key":"ref_77","doi-asserted-by":"crossref","unstructured":"Frerichs, L.M., Frerichs, B., Petzsch, P., Kohrer, K., Windolf, J., Bittersohl, B., Hoffmann, M.J., and Grotheer, V. (2023). Tumorigenic effects of human mesenchymal stromal cells and fibroblasts on bladder cancer cells. Front. Oncol., 13.","DOI":"10.3389\/fonc.2023.1228185"},{"key":"ref_78","first-page":"e53464","article-title":"Measurement and Analysis of Extracellular Acid Production to Determine Glycolytic Rate","volume":"106","author":"Mookerjee","year":"2015","journal-title":"J. Vis. Exp."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"9251303","DOI":"10.1155\/2017\/9251303","article-title":"Arsenite Effects on Mitochondrial Bioenergetics in Human and Mouse Primary Hepatocytes Follow a Nonlinear Dose Response","volume":"2017","author":"Chavan","year":"2017","journal-title":"Oxid. Med. Cell Longev."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"H2068","DOI":"10.1152\/ajpheart.00525.2009","article-title":"Generation of nitric oxide from nitrite by carbonic anhydrase: A possible link between metabolic activity and vasodilation","volume":"297","author":"Aamand","year":"2009","journal-title":"Am. J. Physiol. Heart Circ. Physiol."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1016\/j.neulet.2004.03.094","article-title":"Adenosine\u2019s role in hypercapnia-evoked cerebral vasodilation in the rat","volume":"365","author":"Phillis","year":"2004","journal-title":"Neurosci. Lett."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"226","DOI":"10.1161\/01.STR.8.2.226","article-title":"Local mechanism of CO2 action of cat pial arterioles","volume":"8","author":"Kontos","year":"1977","journal-title":"Stroke"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"907","DOI":"10.1161\/CIRCRESAHA.119.315024","article-title":"Acid-Sensing Ion Channels: Novel Mediators of Cerebral Vascular Responses","volume":"125","author":"Faraci","year":"2019","journal-title":"Circ. Res."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"1031","DOI":"10.1161\/CIRCRESAHA.109.207019","article-title":"Whole Body UVA Irradiation Lowers Systemic Blood Pressure by Release of Nitric Oxide From Intracutaneous Photolabile Nitric Oxide Derivates","volume":"105","author":"Volkmar","year":"2009","journal-title":"Circ. Res."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/25\/23\/13013\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T16:46:17Z","timestamp":1760114777000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/25\/23\/13013"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,12,3]]},"references-count":84,"journal-issue":{"issue":"23","published-online":{"date-parts":[[2024,12]]}},"alternative-id":["ijms252313013"],"URL":"https:\/\/doi.org\/10.3390\/ijms252313013","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,12,3]]}}}