Bone morphogenetic protein (BMP) signalling plays a key role in the control of skin development and postnatal remodelling by regulating keratinocyte proliferation, differentiation and apoptosis. To study the role of BMPs in wound-induced epidermal repair, we used transgenic mice overexpressing the BMP downstream component Smad1 under the control of a K14 promoter as an in vivo model, as well as ex vivo and in vitro assays. K14-caSmad1 mice exhibited retarded wound healing associated with significant inhibition of proliferation and increased apoptosis in healing wound epithelium. Furthermore, microarray and qRT-PCR analyses revealed decreased expression of a number of cytoskeletal/cell motility-associated genes including wound-associated keratins (Krt16, Krt17) and Myo5a, in the epidermis of K14-caSmad1 mice versus wild-type controls during wound healing. BMP treatment significantly inhibited keratinocyte migration ex vivo, and primary keratinocytes of K14-caSmad1 mice showed retarded migration compared to wild-type controls. Finally, siRNA-mediated silencing of Bmpr-1B in primary mouse keratinocytes accelerated cell migration and was associated with increased expression of Krt16, Krt17 and Myo5a compared to controls. Thus, this study demonstrates that BMPs inhibit keratinocyte proliferation, cytoskeletal organization and migration in regenerating skin epithelium during wound healing, and raises a possibility for using BMP antagonists for the management of chronic wounds.
Background: To characterise and compare ocular pathologies presenting to an emergency eye department (EED) during the COVID-19 pandemic in 2020 against an equivalent period in 2019. Methods: Electronic patient records of 852 patients in 2020 and 1818 patients in 2019, attending the EED at a tertiary eye centre (University Hospitals of Leicester, UK) were analysed. Data was extracted over a 31-day period during: (study period 1 (SP1)) COVID-19 pandemic lockdown in UK (24th March 2020–23rd April 2020) and (study period 2 (SP2)) the equivalent 2019 period (24th March 2019–23rd April 2019). Results: A 53% reduction in EED attendance was noted during lockdown. The top three pathologies accounting for >30% of the caseload were trauma-related, keratitis and uveitis in SP1 in comparison to conjunctivitis, trauma-related and blepharitis in SP2. The overall number of retinal tears and retinal detachments (RD) were lower in SP1, the proportion of macula-off RD’s (84.6%) was significantly ( p = 0.0099) higher in SP1 (vs 42.9% in SP2). Conclusion: COVID-19 pandemic related lockdown has had a significant impact on the range of presenting conditions to the EED. Measures to stop spread of COVID-19 such as awareness of hand hygiene practices, social distancing measures and school closures could have an indirect role in reducing spread of infective conjunctivitis. The higher proportion of macula-off RD and lower number of retinal tears raises possibility of delayed presentation in these cases. Going forward, we anticipate additional pressures on EED and other subspecialty services due to complications and associated morbidity from delayed presentations.
Using Herovici staining and digital image analysis, we have studied the collagen subtype and fiber orientation in mature burn scars. These techniques have shown mature burn scars to have increased type I/type III collagen ratios compared with normal skin. Additionally, the collagen orientation of burn scars has been shown to be thickened, tightly packed, and lacking the "basket weave" appearance of normal skin specimens. These techniques allow the differentiation of type I collagen from type III collagen, the assessment of collagen orientation, and the analysis of scar architecture in terms of epidermis and papillary/reticular dermis contribution. These findings are important clinically because collagen subtype and fiber orientation may predict future scar activity. Any attempt to modify the scarring process can be directly measured and compared using this easily reproducible technique.
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