On the contrary there was no difference in CD3+, CD8+, CD20+, CD68+ expression when comparing cSCC in patients with recessive dystrophic epidermolysis bullosa to cSCC in renal transplant recipients .
Taken together, our work provides a framework for efficient, precise, and safe repair of COL7A1, which lies at the heart of a future curative therapy of RDEB.
To overcome these limitations, we applied an A•T→G•C adenine base editor (ABE) to correct two different COL7A1 mutations in primary fibroblasts derived from RDEB patients.
Recessive dystrophic epidermolysis bullosa (RDEB) is a debilitating genodermatosis caused by loss-of-function mutations in COL7A1 encoding type VII collagen (C7), the main component of anchoring fibrils at the dermal-epidermal junction.
We developed a self-inactivating lentiviral platform encoding a codon-optimized COL7A1 cDNA under the control of a human phosphoglycerate kinase promoter for phase I evaluation.METHODSIn this single-center, open-label phase I trial, 4 adults with RDEB each received 3 intradermal injections (~1 × 106 cells/cm2 of intact skin) of COL7A1-modified autologous fibroblasts and were followed up for 12 months.
In recessive dystrophic epidermolysis bullosa (RDEB), biallelic mutations of the gene COL7A1, encoding for collagen VII, the main component of anchoring fibrils, lead to a loss of collagen VII in the extracellular matrix (ECM).
Recessive Dystrophic Epidermolysis Bullosa (RDEB) is a monogenetic inherited genodermatosis associated with deleterious mutations in the gene encoding type VII collagen (COL7A1).
Our strategy could potentially be extended to a large number of COL7A1 mutation-bearing exons within the long collagenous domain of this gene, opening the way to precision medicine for RDEB.
Comparison of PLK1 siRNA with MEK inhibition, AKT inhibition, and the microtubule-disrupting agent vinblastine in RDEB SCC shows that only PLK1 reduction exhibits a similar sensitivity profile to rigosertib.
Comparison of PLK1 siRNA with MEK inhibition, AKT inhibition, and the microtubule-disrupting agent vinblastine in RDEB SCC shows that only PLK1 reduction exhibits a similar sensitivity profile to rigosertib.
Recessive dystrophic epidermolysis bullosa (RDEB) is a skin fragility disorder caused by mutations in the COL7A1 gene encoding type VII collagen, a cutaneous basement membrane component essential for epidermal-dermal adhesion.
In patients with RDEB, miR-145-5p is overexpressed in RDEB skin fibroblasts (RDEBFs), where it plays a profibrotic role, as its inhibition reduces RDEBF fibrotic traits (contraction, proliferation and migration). miR-145-5p inhibition in RDEBFs determines the reduction of contractile markers α-smooth muscle actin and transgelin through upregulation of Krüppel-like factor 4, a transcriptional repressor of contractile proteins, and downregulation of Jagged1 (JAG1), an inducer of fibrosis.What is the translational message?
In patients with RDEB, miR-145-5p is overexpressed in RDEB skin fibroblasts (RDEBFs), where it plays a profibrotic role, as its inhibition reduces RDEBF fibrotic traits (contraction, proliferation and migration). miR-145-5p inhibition in RDEBFs determines the reduction of contractile markers α-smooth muscle actin and transgelin through upregulation of Krüppel-like factor 4, a transcriptional repressor of contractile proteins, and downregulation of Jagged1 (JAG1), an inducer of fibrosis.What is the translational message?
In patients with RDEB, miR-145-5p is overexpressed in RDEB skin fibroblasts (RDEBFs), where it plays a profibrotic role, as its inhibition reduces RDEBF fibrotic traits (contraction, proliferation and migration). miR-145-5p inhibition in RDEBFs determines the reduction of contractile markers α-smooth muscle actin and transgelin through upregulation of Krüppel-like factor 4, a transcriptional repressor of contractile proteins, and downregulation of Jagged1 (JAG1), an inducer of fibrosis.What is the translational message?
Recessive dystrophic epidermolysis bullosa (RDEB), Kindler syndrome (KS) and xeroderma pigmentosum complementation group C (XPC) are three genodermatoses with high predisposition to cancer development.
Knockdown of TSP1 reduced phosphorylation of smad3 (a downstream target of TGF-β signaling) in RDEB primary fibroblasts, whereas overexpression of collagen VII reduced phosphorylation of smad3.