TMPRSS11a is a novel age‐altered, tissue specific regulator of migration and wound healing

Abstract

Aging is a gradual biological process characterized by a decrease in cellular and organism functions. Aging-related processes involve changes in the expression and activity of several proteins. Here, we identified the transmembrane protease serine 11a (TMPRSS11a) as a new age-specific protein that plays an important role in skin wound healing. TMPRSS11a levels increased with age in rodent and human skin and gingival samples. Strikingly, overexpression of TMPRSS11a decreased cell migration and spreading, and inducing cellular senescence. Mass spectrometry, bioinformatics, and functional analyses revealed that TMPRSS11a interacts with integrin β 1 through an RGD sequence contained within the C-terminal domain and that this motif was relevant for cell migration. Moreover, TMPRSS11a was associated with cellular senescence, as shown by overexpression and downregulation experiments.In agreement with tissue-specific expression of TMPRSS11a, shRNA-mediated downregulation of this protein improved wound healing in the skin, but not in thePlasmids encoding mouse TMPRSS11a (MYC-DDK-tagged, #MR220783) and human TMPRSS11a (MYC-DDK-tagged, #RC221395) were purchased from Origene, Rockville, MD. Plasmids encoding human TMPRSS11a-EGFP was purchased from GenScript, Piscataway, NJ. USA. Beta-1 integrin-mCherry was kindly provided by Dr Davidson (via Addgene plasmid #55064). Empty vectors pcDNA4/TO or EGFP were from Lonza (Bend, USA). skeletal muscle of old mice, where TMPRSS11a is undetectable. Collectively, these findings indicate that TMPRSS11a is a tissue-specific factor relevant for wound healing, which becomes elevated with aging, promoting cellular senescence and inhibiting cell migration and skin repair.

PPI-MASS: An Interactive Web Server to Identify Protein-Protein Interactions From Mass Spectrometry-Based Proteomics Data

“…This protein is a Type II transmembrane serine protease (TTSP) participating in diverse biological processes. As reported recently by our group, a differentiated expression of TMPRSS11a with age was identified in gingival and skin fibroblasts, which has been associated with senescence processes and wound healing (Fernandez et al, 2021). Moreover, it was demonstrated that TMPRSS11a participates in critical cellular responses, including cell migration and spreading.…”

“…Interestingly, integrins are recognized targets of proteins containing an arginine-glycine-aspartic acid (RGD) motif ( Moreno-Layseca et al, 2019 ), which was identified in TMPRSS11a. Considering this evidence, protein-protein docking, and molecular dynamics simulations were performed, identifying a favored TMPRSS11a:Integrin complex detailed at Fernandez et al, 2021 . The physical association of both proteins was predicted to occur between the RGD motif of TMPRSS11a and a pocket located at the top face of the α 5 β 1 integrin.…”

Relationship Between Endothelial and Angiogenesis Biomarkers Envisage Mortality in a Prospective Cohort of COVID-19 Patients Requiring Respiratory Support

“…Migration was allowed to occur for 24 h. Following the removal of the non-invading cells, the invading cells were fixed and stained with 0.2% crystal violet. Cell migration was evaluated by counting five (× 20) fields per chamber ( 29 ).…”

Molecular characterization of chronic cutaneous wounds reveals subregion‐ and wound type‐specific differential gene expression

“…These mediators have been implicated both in the recruitment of neutrophils into the epidermis and the presence of p21-induced cellular senescence and thus may have a negative impact on wound re-epithelialization. [84][85][86] Pairwise comparisons between ulcer types resulted in enrichment of certain pathways in LUs, including those reflecting elevated levels of inflammatory activity, hypoxia, and reperfusion. These responses may induce an adaptive response that results in an increased rate of glycolysis in order to conserve energy or promote cell death.…”