Objective: To analyze the correlation between integrin β₁, focal adhesion kinase (FAK), extracellular signal-regulated kinase 1/2 (ERK1/2) of hypertrophic scar (HS) and post injury time in burn patients in scar remodeling stage. Methods: Thirty-four patients with 34 HS specimens admitted to Department of Burns and Plastic Surgery of Chengdu No.2 Hospital and Institute of Burn Research of the First Affiliated Hospital of Army Medical University (originally the Third Military Medical University) from May 2013 to April 2016 were recruited by convenient sampling method, and normal skin specimens were obtained from donor sites of another 6 patients from the above-mentioned departments who had scar resection and skin grafting for this cross-sectional and observational study. Vancouver Scar Scale (VSS) was used to assess the height, vascularity, pigmentation, and pliability of scars. Diasonograph was used to assess scar thickness. Immunohistochemical method was used to observe the expressions of integrin β₁, FAK, and ERK1/2 in dermis and epidermis of scar and normal skin. Correlations between the post injury time and the scar thickness, the post injury time and the expressions of integrin β₁, FAK, and ERK1/2 in epidermis of scar, the post injury time and the expressions of integrin β₁, FAK, and ERK1/2 in dermis of scar, the expressions of integrin β₁, FAK, and ERK1/2 in dermis and those in epidermis of scar were analyzed by Pearson correlation analysis. Locally estimated scatterplot smoothing curve fitting line was used to demonstrate the non-linear regression relationship between the expressions of integrin β₁, FAK, and ERK1/2 in dermis and those in epidermis of scar, the scar thickness and the post injury time. Results: (1) The total VSS score of scars of patients was (8.3±2.3) points, with height scored (2.2±0.7) points, vascularity scored (2.0±0.8) points, pigmentation scored (2.3±0.7) points, and pliability scored (1.9±0.7) points. The thickness of scar was (2.8±1.1) mm. (2) The expressions of integrin β₁, FAK, and ERK1/2 in dermis and epidermis of scar were more than those in normal skin. (3) There was significantly positive correlation between the scar thickness and the post injury time (r=0.39, P<0.05). There was significantly positive correlation between the expression of integrin β₁ in epidermis of scar and the post injury time (r=0.33, P<0.05). There were no significantly correlations between the expressions of FAK and ERK1/2 in epidermis of scar and the post injury time (r=-0.03, -0.04, P>0.05). There was significantly negative correlation between the expression of FAK in dermis of scar and the post injury time (r=-0.34, P<0.05). There were no significantly correlations between the expressions of integrin β₁ and ERK1/2 in dermis of scar and the post injury time (r=0.07, -0.23, P>0.05). There were significantly positive correlation between the expressions of integrin β₁, FAK, and ERK1/2 in dermis and those in epidermis of scar (r=0.70, 0.60, 0.64, P<0.01). (4) The expressions of integrin β₁, FAK, and ERK1/2 in dermis and epidermis of scar were changed from downtrend in 1 to 2 months post injury to uptrend in 2 to 3 months post injury, which reached the peak around 3 to 4 months post injury. Hereafter the expressions of mechanical signaling molecules in epidermis of scar were gradually declined, while the expressions of mechanical signaling molecules in dermis of scar were at a quite high level within half a year post injury. Scar thickness was steadily increased after 1 month post injury. Conclusions In scar remodeling stage of burn patients, the HS thickness increases continuously along with the increasing post injury time in the early stage of scar formation. The vulnerability of integrin β₁, FAK, and ERK1/2 of HS to external mechanical stimuli increases gradually within 4 months post injury.

NDFIP1 has been previously reported as a tumor suppressor in multiple solid tumors, but the function of NDFIP1 in NSCLC and the underlying mechanism are still unknown. Besides, the WW domain containing proteins can be recognized by NDFIP1, resulted in the loading of the target proteins into exosomes. However, whether WW domain-containing transcription regulator 1 (WWTR1, also known as TAZ) can be packaged into exosomes by NDFIP1 and if so, whether the release of this oncogenic protein via exosomes has an effect on tumor development has not been investigated to any extent. Here, we first found that NDFIP1 was low expressed in NSCLC samples and cell lines, which is associated with shorter OS. Then, we confirmed the interaction between TAZ and NDFIP1, and the existence of TAZ in exosomes, which requires NDFIP1. Critically, knockout of NDFIP1 led to TAZ accumulation with no change in its mRNA level and degradation rate. And the cellular TAZ level could be altered by exosome secretion. Furthermore, NDFIP1 inhibited proliferation in vitro and in vivo, and silencing TAZ eliminated the increase of proliferation caused by NDFIP1 knockout. Moreover, TAZ was negatively correlated with NDFIP1 in subcutaneous xenograft model and clinical samples, and the serum exosomal TAZ level was lower in NSCLC patients. In summary, our data uncover a new tumor suppressor, NDFIP1 in NSCLC, and a new exosome-related regulatory mechanism of TAZ.
Humans ; Carcinoma, Non-Small-Cell Lung/metabolism* ; Carrier Proteins/metabolism* ; Cell Line ; Cell Proliferation ; Exosomes/metabolism* ; Lung Neoplasms/genetics* ; Membrane Proteins/metabolism* ; Transcriptional Coactivator with PDZ-Binding Motif Proteins/metabolism*