Dysfunctional Latent Transforming Growth Factor β Activation After Corneal Injury in a Classical Ehlers-Danlos Model

Matrix Biol. 2024 Feb 8:S0945-053X(24)00023-4. doi: 10.1016/j.matbio.2024.02.004. Online ahead of print.ABSTRACTPatients with classical Ehlers Danlos syndrome (cEDS) suffer impaired wound healing and from scars formed after injuries that are atrophic and difficult to close surgically. Haploinsufficiency in COL5A1 creates systemic morphological and functional alterations in the entire body. We investigated mechanisms that impair wound healing from corneal lacerations (full thickness injuries) in a mouse model of cEDS (Col5a1+/-). We found that collagen V reexpression in this model is upregulated during corneal tissue repair and that wound healing is delayed, impaired, and results in large atrophic corneal scars. We noted that in a matrix with a 50% content of collagen V, activation of latent Transforming Growth Factor (TGF) β is dysregulated. Corneal myofibroblasts with a haploinsufficiency of collagen V failed to mechanically activate latent TGF β. Second harmonic imaging microscopy showed a disorganized, undulated, and denser collagen matrix in our Col5a1+/- model that suggested alterations in the extracellular matrix structure and function. We hypothesize that a regenerated collagen matrix with only 50% content of collagen V is not resistant enough mechanically to allow adequate activation of latent TGF β by fibroblasts and myofibroblasts.PMID:38340967 | DOI:10.1016/j.matbio.2024.02.004
Source: Matrix Biology - Category: Molecular Biology Authors: Source Type: research