Biology subjects

Kurinna, S.

Publications and source records attributed to Kurinna, S..

3 recordsLinked to original sources

bioRxiv2026

Quantitative Spatial Analysis of Matrix Remodelling in Wounds Using Digital Pathology and Fractal Analysis

Wound healing involves spatially heterogeneous changes in matrix composition and organisation that can be difficult to capture using qualitative histological assessment alone. We developed a reproducible digital pathology workflow to quantify matrix features in cutaneous wound sections, compare them with unwounded skin, and derive an exploratory Histological Wound Index (HWI). Four normal-skin and six wound sections were analysed using QuPath, ImageJ/FracLac and Python. Approximately 500 x 500 micrometer regions of interest (ROI) were assigned to normal skin, wound centre, proximal edge or distant edge. Collagen, mucin and necrotic tissue coverage were quantified using image classifiers and analysed with linear mixed-effects models. Collagen architecture was assessed from collagen-selective binary masks using fractal dimension and lacunarity. Collagen coverage, fractal dimension, mucin coverage, necrosis and lacunarity were z-standardised and integrated into the HWI. Unwounded skin showed high collagen coverage and fractal dimension, with low lacunarity, mucin and necrosis. In contrast, wound-centre tissue showed low collagen coverage and fractal dimension together with higher mucin and necrosis. Distant-edge regions retained comparatively normal-like characteristics, whereas proximal-edge regions showed intermediate values. HWI was highest in normal skin and lowest in the wound centre. A descriptive matched-ROI comparison of two wound sections reproduced this regional ordering when all component measures were derived from identical ROI boundaries. This workflow provides a reproducible framework for quantifying regional ECM features and collagen-mask architecture in wound histology. The HWI is an exploratory histological summary requiring validation in larger longitudinal datasets.

bioinformatics↗

bioRxiv2024

miRNA-29-CLIP uncovers new targets and functions to improve skin repair

MicroRNAs (miRNAs) control organogenesis in mammals but their role in specific cell types is not fully explored. miRNAs exert their function by binding mRNAs and inhibiting translation. Skin is an excellent model to study the role of miRNAs in primary cells of epidermal (keratinocytes) and mesodermal (fibroblasts) origin, because the growth of these cells is tightly controlled at translation. Previous research demonstrated that miRNA-29 family functions during skin repair, however, the exact mRNA targets and the downstream mechanisms of miRNA-29-mediated regulation of cell growth is missing. Here, we use miRNA crosslinking and immunoprecipitation (miRNA-CLIP) method to find the direct targets of miRNA-29 in keratinocytes and fibroblasts from human skin. We uncover previously unrecognized roles of miRNA-29 in protein folding and RNA processing, common to all cell types tested, and determine the cell-specific role of miRNA-29. Using modified anti-sense oligonucleotides (ASO) in 2D and 3D cultures of keratinocytes and fibroblasts, we enhanced cell-to-matrix adhesion and found an autocrine and paracrine mechanism of miRNA-29-dependent cell growth. Our results include a comprehensive list and functional analyses of mRNAs directly bound by miRNA-29 keratinocytes and fibroblasts, determined by miRNA-CLIP and ASO-mediated inhibition of miRNA-29 followed by RNA-seq. We reveal a full transcriptome of human keratinocytes with enhanced adhesion to the wound matrix, which supports regeneration of the epidermis and is regulated by miRNA-29. The functions of miRNA-29 identified in this study can provide a new approach to improve cutaneous repair by restoring and enhancing the endogenous mechanisms through the stage-specific delivery of miRNA-29 ASO.

cell biology↗

bioRxiv2022

miR targetome of primary human keratinocytes reveals a function for non-conserved binding sites

The homeostasis of the human body is protected by the skin, where the process of keratinocyte differentiation in outer layers has a crucial role. Cessation of proliferation in the basal layer of keratinocytes and initiation of their subrabasal functions are tightly controlled at the level of gene transcription and message translation. A subset of mRNAs has to be repressed during differentiation, and microRNAs are known to contribute to this by directly binding mRNAs at the 3UTRs. Using results of RNA sequencing from human primary keratinocytes during induced differentiation, we evaluated the predicted binding of highly, moderately, and lowly expressed miRs to their target mRNAs. We found that moderately expressed miRs can regulate more mRNAs, and that they do so using both conserved and non-conserved canonical binding. The cumulative score for the majority of repressed mRNAs revealed a surprisingly weak binding to miRs, and we found a significant contribution of non-conserved sites to the repression of the targets. While the presence of at least one conserved site was necessary for the miR function, its weak binding may be reinforced by a non-conserved site. Together, we found that the combination of conserved and non-conserved sites lower the binding threshold for miR-mRNA interactions to assume a tighter repression of the mRNA target during cell differentiation.

molecular biology↗