Biochemical Basis of Collagen Defect: Keloids
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Abstract
Obscure in their genesis, keloids are benign fibro-proliferative disorders. They take place as a result of disturbances in the typical wound healing process in vulnerable people. Transforming Growth Factor beta (TGF-ß) family members have been linked to the pathogenesis of this illness, despite the fact that many other factors have been hypothesized to contribute to its aetiopathogenesis. Finding the right therapeutical notion requires understanding the differences between hypertrophic scars, keloids, and typical scars. Even though keloids are rather common in the general population, the mechanisms that cause keloid formation are still poorly understood. The fact that there are numerous treatment modalities reflects the reality that no single treatment has consistently demonstrated to be highly successful. New pathophysiological theories for keloid formation are revealed by improvements in our understanding of the wound healing process. This review distinguishes between keloids and hypertrophic scars, provides an overview of physiological wound healing, examines current theories for keloid formation, and describes the etiology of scar formation. This knowledge could aid in unraveling the complicated keloid etiology and aid in the creation of a successful treatment approach.
Keywords:
Keloids; TGF-ß; Fibroplasia; Extracellular matrix; Tissue inhibitor of metalloproteinase; Plasminogen activator inhibitor
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Ale, E. M., Asuelimen, S. O., Andeuka, U. A., Umaru, I. J., & Umaru, K. I. (2024). Biochemical Basis of Collagen Defect: Keloids. African Journal of Biochemistry and Molecular Biology Research, 1(1), 667-692. https://doi.org/10.58578/ajbmbr.v1i1.3704
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Appleton I, Brown NJ and Willoughby D.A. (1996): Apoptosis, necrosis and proliferation: possible implication in the etiology of keloids. Am J Pathol 149: 1441-1447.
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Atiyeh BS, Costagliola M and Hayek S.N. (2005): Keloid or hypertrophic scar: the controversy: review of literature. Ann Plast Surg 54: 676-680.
Baisch A and Riedel F. (2006): Hyperplastic scars and keloids: Part I: Basics and prevention. HNO 54: 893-905.
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Bayat A, Arscott G, Ollier WE, Ferguson MW and McGrouther D.A. (2003): ‘Aggressive keloid’: a severe variant of familial keloid scarring. J R Soc Med 96: 554-555.
Bayat A, Arscott G, Ollier WE, McGrouther DA and Ferguson M.W. (2005). Keloid disease: clinical relevance of single versus multiple site scars. Br J Plast Surg. 58(1): 28-37.
Bayat A, Arscott G, Ollier WER, Ferguson MWJ and Mc Grouther D.A. (2004). Description of site-specific morphology of keloid phenotypes in an Afrocaribbean population. British Journal of Plastic Surgery. 57(2): 122-133.
Bayat A, Bock O, Mrowietz U, Ollier WE and Ferguson M.W. (2002). Genetic susceptibility to keloid disease and transforming growth factor beta 2 polymorphisms. Br J Plast Surg 55: 283-286.
Bayat A, Bock O, Mrowietz U, Ollier WER and Ferguson MWJ. (2004). Genetic susceptibility to keloid disease: Transforming growth factor beta1 receptor gene polymorphisms are not associated with keloid disease. Experimental Dermatology. 13(2): 120-124.
Bayat A, McGrouther DA and Ferguson MWJ. (2003). Skin scarring. British Medical Journal. 326(7380): 88-92.
Berman B and Flores F. (1998). The treatment of hypertrophic scars and keloids. Eur J Dermatol. 8(8): 591-5.
Bianca C. (2011). mathematical modeling for keloid formation triggered by virus: malignant effects and immune system competition. Mathematical Models and Methods in Applied Sciences. 21(02): 389-419.
Bock O and Mrowietz U. (2002). Keloide - Eine dermale fibroproliferative Erkrankung unbekannter Ursache. Der Hautarzt 53: 515-523.
Bock O, Schmsid-Ott G, Malewski P and Mrowietz U. (2006). Quality of life of patients with keloid and hypertrophic scarring. Arch Dermatol Res 297: 433-438.
Border WA and Noble NA. (1994). Transforming growth factor beta in tissue fibrosis. N Engl J Med 331:1286-1292.
Brody GS, Peng ST and Landel R.F. (1981). The etiology of hypertrophic scar contracture: another view. Plast Reconstr Surg 67: 673-684.
Brown JJ and Bayat A. (2009). Genetic susceptibility to raised dermal scarring. British Journal of Dermatology. 161(1): 8-18.
Burd A and Huang L. (2005). Hypertrophic response and keloid diathesis: two very different forms of scar. Plast Reconstr Surg 116: 150e-157e.
Butler PD, Longaker MT and Yang G.P. (2008). Current progress in keloid research and treatment. J Am Coll Surg 206: 731-741.
Butler PD, Longaker MT and Yang GP. (2008). Current Progress in Keloid Research and Treatment. Journal of the American College of Surgeons. 206(4): 731-741
Calnan JS and Copenhagen H.J. (1967). Autotransplantation of keloid in man. Br J Surg 54: 330-335.
Campaner AB, Ferreira LM, Gragnani A, Bruder JM, Cusick JL and Morgan J.R. (2006). Upregulation of TGF-beta expression may be necessary but is not sufficient for excessive scarring. J Invest Dermatol 126: 1168-1176.
Chike-Obi CJ, Cole PD and Brissett A.E. (2009). Keloids: pathogenesis, clinical features, and management. Semin Plast Surg. 23(3): 178-84.
Chin GS, Liu W, Peled Z, Lee TY, Steinbrech DS, Hsu M and Longaker M.T. (2001). Differential expression of transforming growth factor-beta receptors I and II and activation of Smad 3 in keloid fibroblasts. Plast Reconstr Surg 108: 423-429.
Chung JH, Seo JY, Choi HR, Lee MK, Youn CS and Rhie G. (2001). Modulation of skin collagen metabolism in aged and photoaged human skin in vivo. J Invest Dermatol. 117(5): 1218-24.
Clark JA, Cheng JC and Leung K.S. (1996). Mechanical properties of normal skin and hypertrophic scars. Burns. 22(6): 443-6.
Clark JA, Turner ML, Howard L, Stanescu H, Kleta R and Kopp J.B. (2009). Description of familial keloids in five pedigrees: evidence for autosomal dominant inheritance and phenotypic heterogeneity. BMC Dermatol. 9(8): 1471-5945.
Clark R.A. (2001). Fibrin and wound healing. Ann NY Acad Sci 936: 355-367.
Cole J, Tsou R, Wallace K, Gibran N and Isik F. (2001). Comparison of normal human skin gene expression using cDNA microarrays. Wound Repair Regen 9: 77-85.
Davidson S, Aziz N, Rashid RM and Khachemoune A. (2009). A primary care perspective on Keloids. MedGenMed Medscape General Medicine. 11(1).
Diegelmann RF and Evans M.C. (2004). Wound healing: an overview of acute, fibrotic and delayed healing. Front Biosci 9: 283-289.
Diegelmann RF, Cohen IK and Kaplan A.M. (1981). The role of macrophages in wound repair: a review. Plast Reconstr Surg 68: 107-113.
Eckes B, Zigrino P, Kessler D, Holtkötter O, Shephard P, Mauch C and Krieg T. (2000): Fibroblast-matrix interactions in wound healing and fibrosis. Matrix Biol 19: 325-332.
Fong EP and Bay BH:(2002). Keloids - the sebum hypothesis revisited. Med Hypotheses 58: 264-269,
Fujiwara M, Muragaki Y and Ooshima A. (2005): Keloid-derived fibroblasts show increased secretion of factors involved in collagen turnover and depend on matrix metalloproteinase for migration. Br J Dermatol 153: 295-200.
Gauglitz GG, Korting HC, Pavicic T, Ruzicka T and Jeschke M.G. (2011). Hypertrophic scarring and keloids: Pathomechanisms and current and emerging treatment strategies. Molecular Medicine. 17(1-2): 113-125.
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