Background
Methods
Transcriptomic data
Normalization and quality check
Data analysis
Pathway enrichment analysis using eSkIN
Comparative pathway enrichment analysis using DAVID
Results
Gene/Pathway | Role in skin pathways | Impact derived from eSkIN |
---|---|---|
TNF pathway | TNF pathway via NF-κB regulates the transcription of inflammatory cytokines, adhesion molecules, MMP9 and SELE. | TNF and its receptors are downregulated after treatment with BM, thus effecting anti-inflammatory effect. |
TLRs | TLRs play important role in inflammation by activating NF-κB, which in turn, activates inflammatory cytokines. | Downregulated after treatment with BM, thus bringing about anti-inflammatory effect. |
IL4 pathway | Involved in T-cell and eosinophil chemotaxis | Downregulated after treatment with BM, thus contributes towards anti-inflammatory effect. |
LOR, FLG, TGM5 and CDSN | Important skin barrier proteins | Upregulated after treatment with BM; contributes towards restoration of skin barrier functions. |
IVL, Keratins, LCEs, desmocollins and desmogleins | Important skin barrier proteins | Downregulated after treatment with BM representing the damage to skin barrier; CD44, AKT1, PKC-δ, HRAS and MAP2K3 involved in pathway leading to transcriptional activation of barrier proteins are also downregulated in BM samples. |
S100 family proteins | Important anti-microbial peptides that help in protecting the skin from infections. | Downregulated after treatment with BM, thus leading to impaired barrier function. |
VEGF | Wound healing and cell migration, vascular permeability, angiogenesis, cell invasion and coagulation | Downregulated after treatment with BM, thus affecting wound healing and other cellular processes through PLC-γ and MAPK cascade. |
H2AFX, RAD51, BRCA2, MCM3, DHFR, HMOX1, GINS1 and PCNA | Genes involved in DNA repair | Downregulated after treatment with BM, thus affecting DNA repair processes. |
Gene/Pathway | Role in skin pathways | Impact derived from eSkIN |
---|---|---|
TGF-β | Plays important role in inflammation via SMADs, and regulates IFNG, IL2, CCL4, CXCL2 and MMP2 that are involved in T-cell chemotaxis and B-cell maturation | Downregulated after treatment with PC, thus contributes towards anti-inflammatory effect. |
IL13 receptor (IL13RA2) | Important regulator of chemokines through JAK-STAT pathway | Downregulated after treatment with PC, thus contributes towards anti-inflammatory effect. |
LOR, FLG, TGM5 and CDSN | Important skin barrier proteins | Upregulated after treatment with PC, thus contributes towards restoration of barrier functions. |
BM causes large-scale perturbations in inflammatory response as compared to PC
BM mediates its anti-inflammatory effect via TNF, TLRs and IL4 pathways
PC suppresses inflammation via IL13, IL6 and VEGF pathways
Additional pathways responsible for anti-inflammatory effect of BM and PC
Restoration of skin barrier by BM and PC
BM adversely affects the synthesis of barrier proteins through AP1 family and CEBPs
Additional pathways responsible for effect on skin barrier by BM and PC
Cellular functions affected by BM and PC
Comparison of eSkIN results with DAVID
Comparison of pathway enrichment for BM dataset
S.No. | Important pathways enriched in eSkIN | Related processes/pathways enriched in BM samples | Related processes/pathways enriched in PC samples | ||
---|---|---|---|---|---|
GO_BP_FAT | KEGG | GO_BP_FAT | KEGG | ||
1. | Keratinocyte differentiation, Cornification, Basal layer formation | keratinocyte differentiation, skin development, keratinization, skin epidermis development | – | epidermis development, skin development, keratinocyte differentiation, epidermal cell differentiation, keratinization | – |
2. | Inflammation | inflammatory response, regulation of inflammatory response, T-cell activation | TNF signaling pathway, NF-κB signaling pathway, Inflammatory bowel disease | – | – |
3. | Immune response | Immune response, defense response, Innate immune response | – | Immune response, defense response, Innate immune response | – |
4. | Chemokine signaling | Chemokine mediated signaling pathway and chemokine production | Chemokine signaling pathway, Cytokine-cytokine receptor interaction | – | – |
5. | DNA Damage and Repair | DNA integrity checkpoint | – | – | – |
6. | Cell Adhesion, Cell Migration | Cell adhesion, leukocyte cell-cell adhesion, cell migration, regulation of cell migration, leukocyte migration | Cell adhesion molecules (CAMs) | Cell migration, leukocyte migration | – |