Incubation with porcine urinary bladder matrix yields a late-stage wound transcriptome in endothelial cells and keratinocytes isolated from both diabetic and non-diabetic subjects

Authors

John T. Paige, LSU Health Sciences Center - New OrleansFollow
Daniel J. Lightell, Tulane University School of Medicine, New Orleans, LA
Hunter F. Douglas, Tulane University School of Medicine, New Orleans, LA
Natasha C. Klingenberg, Tulane University School of Medicine, New Orleans, LA
Thaidan Pham, Tulane University School of Medicine, New Orleans, LA
T. Cooper Woods, Tulane University School of Medicine, New Orleans, LA

Document Type

Article

Publication Date

6-15-2023

Publication Title

Experimental Dermatology

Abstract

Proper wound closure requires the functional coordination of endothelial cells (ECs) and keratinocytes. In the late stages of wound healing, keratinocytes become activated and ECs promote the maturation of nascent blood vessels. In diabetes mellitus, decreased keratinocyte activation and impaired angiogenic action of ECs delay wound healing. Porcine urinary bladder matrix (UBM) improves the rate of wound healing, but the effect of exposure to UBM under diabetic conditions remains unclear. We hypothesized that keratinocytes and ECs isolated from both diabetic and non-diabetic donors would exhibit a similar transcriptome representative of the later stages of wound healing following incubation with UBM. Human keratinocytes and dermal ECs isolated from non-diabetic and diabetic donors were incubated with and without UBM particulate. RNA-Seq analysis was performed to identify changes in the transcriptome of these cells associated with exposure to UBM. While diabetic and non-diabetic cells exhibited different transcriptomes, these differences were minimized following incubation with UBM. ECs exposed to UBM exhibited changes in the expression of transcripts suggesting an increase in the endothelial–mesenchymal transition (EndoMT) associated with vessel maturation. Keratinocytes incubated with UBM demonstrated an increase in markers of activation. Comparison of the whole transcriptomes with public datasets suggested increased EndoMT and keratinocyte activation following UBM exposure. Both cell types exhibited loss of pro-inflammatory cytokines and adhesion molecules. These data suggest that application of UBM may accelerate healing by promoting a transition to the later stages of wound healing. This healing phenotype is achieved in cells isolated from both diabetic and non-diabetic donors.

First Page

1430

Last Page

1438

PubMed ID

37317944

Volume

32

Issue

9

Creative Commons License

This work is licensed under a Creative Commons Attribution-NonCommercial-No Derivative Works 4.0 International License.

Recommended Citation

Paige, John T.; Lightell, Daniel J.; Douglas, Hunter F.; Klingenberg, Natasha C.; Pham, Thaidan; and Woods, T. Cooper, "Incubation with porcine urinary bladder matrix yields a late-stage wound transcriptome in endothelial cells and keratinocytes isolated from both diabetic and non-diabetic subjects" (2023). School of Medicine Faculty Publications. 2046.
https://digitalscholar.lsuhsc.edu/som_facpubs/2046
10.1111/exd.14845