Search Results (3)

(1) Background: As society progresses, increasing numbers of individuals are experiencing hair loss, which can be attributed to factors such as unhealthy diets, insufficient sleep, stress, and hormonal imbalances. Currently available pharmacological treatments for hair loss often cause undesirable side effects, highlighting the urgent need to explore safer and more effective agents to promote hair restoration. This study investigated the role of recombinant human type XVII collagen derived from the α1 chain (rhCOL17A1) in facilitating hair growth and restoration. (2) Methods: We analyzed the impact of rhCOL17A1 on the mRNA expression of several growth factors, as well as Bcl-2 and Bax, at the cellular level. Moreover, the effects of rhCOL17A1 on the expression of key proteins in the Wnt/β-catenin and Sonic Hedgehog (SHH)/GLI signaling pathways were examined by Western blotting (WB). At the organismal level, we established a model in C57BL/6 mice through chronic subcutaneous administration of 5% testosterone propionate. We subsequently assessed the effect of rhCOL17A1 on hair regrowth via histological analysis using hematoxylin and eosin (H&E) staining and immunofluorescence staining. (3) Results: rhCOL17A1 contributes to the resistance of hair follicle dermal papilla cells (HFDPCs) to apoptosis. rhCOL17A1 activates the Wnt/β-catenin and SHH/GLI signaling pathways, and increases the expression of type XVII collagen (COLXVII), thereby creating a favorable environment for hair growth. Furthermore, rhCOL17A1 exerts a significant growth-promoting effect at the animal level. (4) Conclusions: rhCOL17 promotes hair growth by activating the Wnt/β-catenin and SHH/GLI signaling pathways and upregulating COLXVII expression. Full article

Epidermolysis bullosa (EB), characterized by defective adhesion of the epidermis to the dermis, is a heterogeneous disease with many subtypes in human patients and domestic animals. We investigated two unrelated cats with recurring erosions and ulcers on ear pinnae, oral mucosa, and paw pads that were suggestive of EB. Histopathology confirmed the diagnosis of EB in both cats. Case 1 was severe and had to be euthanized at 5 months of age. Case 2 had a milder course and was alive at 11 years of age at the time of writing. Whole genome sequencing of both affected cats revealed independent homozygous variants in COL17A1 encoding the collagen type XVII alpha 1 chain. Loss of function variants in COL17A1 lead to junctional epidermolysis bullosa (JEB) in human patients. The identified splice site variant in case 1, c.3019+1del, was predicted to lead to a complete deficiency in collagen type XVII. Case 2 had a splice region variant, c.769+5G>A. Assessment of the functional impact of this variant on the transcript level demonstrated partial aberrant splicing with residual expression of wildtype transcript. Thus, the molecular analyses provided a plausible explanation of the difference in clinical severity between the two cases and allowed the refinement of the diagnosis in the affected cats to JEB. This study highlights the complexity of EB in animals and contributes to a better understanding of the genotype-phenotype correlation in COL17A1-related JEB. Full article

Junctional epidermolysis bullosa (JEB) is a severe blistering skin disease caused by mutations in genes encoding structural proteins essential for skin integrity. In this study, we developed a cell line suitable for gene expression studies of the JEB-associated COL17A1 encoding type XVII collagen (C17), a transmembrane protein involved in connecting basal keratinocytes to the underlying dermis of the skin. Using the CRISPR/Cas9 system of Streptococcus pyogenes we fused the coding sequence of GFP to COL17A1 leading to the constitutive expression of GFP-C17 fusion proteins under the control of the endogenous promoter in human wild-type and JEB keratinocytes. We confirmed the accurate full-length expression and localization of GFP-C17 to the plasma membrane via fluorescence microscopy and Western blot analysis. As expected, the expression of GFP-C17^mut fusion proteins in JEB keratinocytes generated no specific GFP signal. However, the CRISPR/Cas9-mediated repair of a JEB-associated frameshift mutation in GFP-COL17A1^mut-expressing JEB cells led to the restoration of GFP-C17, apparent in the full-length expression of the fusion protein, its accurate localization within the plasma membrane of keratinocyte monolayers as well as within the basement membrane zone of 3D-skin equivalents. Thus, this fluorescence-based JEB cell line provides the potential to serve as a platform to screen for personalized gene editing molecules and applications in vitro and in appropriate animal models in vivo. Full article