Tauroursodeoxycholic Acid Decreases Keloid Formation by Reducing Endoplasmic Reticulum Stress as Implicated in the Pathogenesis of Keloid

Abstract

Keloids are a common form of pathologic wound healing and are characterized by an excessive production of extracellular matrix. This study examined the major contributing mechanism of human keloid pathogenesis using transcriptomic analysis. We identified the upregulation of mitochondrial oxidative stress response, protein processing in the endoplasmic reticulum, and TGF-β signaling in human keloid tissue samples compared to controls, based on ingenuity pathway and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses. Electron microscopic examinations revealed an increased number of dysmorphic mitochondria and expanded endoplasmic reticulum (ER) in human keloid tissue samples than that in controls. Western blot analysis performed using human tissues suggested noticeably higher ER stress signaling in keloids than in normal tissues. Treatment with tauroursodeoxycholic acid (TUDCA), an ER stress inhibitor, significantly decreased scar formation in rabbit models, compared to normal saline and steroid injections. In summary, our findings demonstrate the contributions of mitochondrial dysfunction and dysregulated ER stress signaling in human keloid formation and the potential of TUDCA in the treatment of keloids.

Quantitative proteomics approach reveals novel biomarkers and pathological mechanism of keloid

“…this was consistent with our current results, and the inhibition of ER stress significantly decreased scar formation in a rabbit model [26].…”

“…In another study, the inhibition of IRE1α also decreased scar formation and decreased XBP1 expression [25]. In a recent study, higher ER stress signaling was demonstrated in keloids than in normal tissues; this was consistent with our current results, and the inhibition of ER stress significantly decreased scar formation in a rabbit model [26]. These results suggested that XBP1, as a key regulator of UPR pathway, is closely related with keloid formation and may represent a potential therapeutic target for keloids.…”

Probiotic-Functionalized Silk Fibroin/Sodium Alginate Scaffolds with Endoplasmic Reticulum Stress-Relieving Properties for Promoted Scarless Wound Healing

“…Similarly, Zhang et al 16 showed that TGF-β1 upregulated the expression of GRP78 and α-SMA in lung fibroblasts, while the ERS inhibitor taurodeoxycholic acid (TUDCA) attenuated the expression of these markers. In keloid tissue in rabbit, Kim et al 39 found that the relief of the ERS could effectively prevent scar formation. Boyko et al 34 reported that inhibition of IRE1 expression could prevent wound scarring.…”

Effects and Mechanism of Particulate Matter on Tendon Healing Based on Integrated Analysis of DNA Methylation and RNA Sequencing Data in a Rat Model

“…Genes with p -values < 0.05 and FC values ≥ 1.2 between the PM and non-PM groups were defined as DEGs. Functional characterization was performed using KEGG and IPA (Ingenuity Systems, Redwood City, CA, USA) to identify pathways with significant p -values and Z-scores [ 57 ]. The GEO submission number is GSE200463.…”