Collagen XII regulates stromal wound closure

Donovan, Christopher; Cogswell, Devon; Sun, Mei; Adams, Sheila M.; Ávila, Marcel Y.; Margo, Curtis E.; Koch, Manuel; Espana, Edgar M.

doi:10.1016/j.exer.2023.109456

Cited by 4 publications

(2 citation statements)

References 39 publications

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“…Acosta et al, 2023, reported the presence of increased LTBP1 expression in murine corneal fibroblasts [ 16 ]. Another recent study found an increased expression of LTBP1 in the keratotomy wounds of mouse corneas [ 67 ]. LTBP2 dysregulation has been linked to eye diseases in numerous studies, including glaucoma [ 68 , 69 , 70 , 71 , 72 , 73 , 74 , 75 , 76 , 77 ].…”

Section: Discussionmentioning

confidence: 99%

Amelioration of Fibrosis via S1P Inhibition Is Regulated by Inactivation of TGF-β and SPL Pathways in the Human Cornea

Nicholas,

Basu,

Mandal

et al. 2024

IJMS

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Human corneal fibrosis can lead to opacity and ultimately partial or complete vision loss. Currently, corneal transplantation is the only treatment for severe corneal fibrosis and comes with the risk of rejection and donor shortages. Sphingolipids (SPLs) are known to modulate fibrosis in various tissues and organs, including the cornea. We previously reported that SPLs are tightly related to both, transforming growth factor beta (TGF-β) signaling and corneal fibrogenesis. The aim of this study was to investigate the effects of sphingosine-1-phosphate (S1P) and S1P inhibition on specific TGF-β and SPL family members in corneal fibrosis. Healthy human corneal fibroblasts (HCFs) were isolated and cultured in EMEM + FBS + VitC (construct medium) on 3D transwells for 4 weeks. The following treatments were prepared in a construct medium: 0.1 ng/mL TGF-β1 (β1), 1 μM sphingosine-1-phosphate (S1P), and 5 μM Sphingosine kinase inhibitor 2 (I2). Five groups were tested: (1) control (no treatment); rescue groups; (2) β1/S1P; (3) β1/I2; prevention groups; (4) S1P/β1; and (5) I2/β1. Each treatment was administered for 2 weeks with one treatment and switched to another for 2 weeks. Using Western blot analysis, the 3D constructs were examined for the expression of fibrotic markers, SPL, and TGF-β signaling pathway members. Scratch assays from 2D cultures were also utilized to evaluate cell migration We observed reduced fibrotic expression and inactivation of latent TGF-β binding proteins (LTBPs), TGF-β receptors, Suppressor of Mothers Against Decapentaplegic homologs (SMADs), and SPL signaling following treatment with I2 prevention and rescue compared to S1P prevention and rescue, respectively. Furthermore, we observed increased cell migration following stimulation with I2 prevention and rescue groups, with decreased cell migration following stimulation with S1P prevention and rescue groups after 12 h and 18 h post-scratch. We have demonstrated that I2 treatment reduced fibrosis and modulated the inactivation of LTBPs, TGF-β receptors, SPLs, and the canonical downstream SMAD pathway. Further investigations are warranted in order to fully uncover the potential of utilizing SphK I2 as a novel therapy for corneal fibrosis.

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Section: Discussionmentioning

confidence: 99%

Amelioration of Fibrosis via S1P Inhibition Is Regulated by Inactivation of TGF-β and SPL Pathways in the Human Cornea

Nicholas,

Basu,

Mandal

et al. 2024

IJMS

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“…In healthy adult tissue, expression is more restricted to collagen I - containing fibrils found in tissues such as bone ( Izu et al, 2011 ; Izu et al, 2016 ; Mondragón et al, 2020 ; Izu and Birk, 2023 ), tendon/ligament ( Izu et al, 2021 ; Fung et al, 2022 ; Izu and Birk, 2023 ), cornea ( Anderson et al, 2000 ; Espana and Birk, 2020 ; Sun et al, 2020 ), and skin ( Berthod et al, 1997 ; Schonborn et al, 2020 ). Expression of collagen XII is also coincident with regenerative processes in a wide range of adult tissues including bone ( Zeitouni et al, 2012 ; McNeill et al, 2020 ), tendon/ligament ( Thomopoulos et al, 2002 ; Tsuzuki et al, 2016 ), cardiac muscle ( Marro et al, 2016 ), skin ( Brant et al, 2015 ; Schonborn et al, 2020 ), cornea ( El-Shabrawi et al, 1998 ; Donovan et al, 2023 ), and even spinal cord ( Wehner et al, 2017 ). In the newt, collagen XII is broadly expressed in the blastema during epimorphic regeneration of appendages ( Wei and Tassava, 1996 ).…”

Section: Introductionmentioning

confidence: 99%

The coordinated activities of collagen VI and XII in maintenance of tissue structure, function and repair: evidence for a physical interaction

Gregory,

Ma,

Lomeli

2024

Front. Mol. Biosci.

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Collagen VI and collagen XII are structurally complex collagens of the extracellular matrix (ECM). Like all collagens, type VI and XII both possess triple-helical components that facilitate participation in the ECM network, but collagen VI and XII are distinct from the more abundant fibrillar collagens in that they also possess arrays of structurally globular modules with the capacity to propagate signaling to attached cells. Cell attachment to collagen VI and XII is known to regulate protective, proliferative or developmental processes through a variety of mechanisms, but a growing body of genetic and biochemical evidence suggests that at least some of these phenomena may be potentiated through mechanisms that require coordinated interaction between the two collagens. For example, genetic studies in humans have identified forms of myopathic Ehlers-Danlos syndrome with overlapping phenotypes that result from mutations in either collagen VI or XII, and biochemical and cell-based studies have identified accessory molecules that could form bridging interactions between the two collagens. However, the demonstration of a direct or ternary structural interaction between collagen VI or XII has not yet been reported. This Hypothesis and Theory review article examines the evidence that supports the existence of a functional complex between type VI and XII collagen in the ECM and discusses potential biological implications.

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