Phospholipase D1 decreases type I collagen levels in hepatic stellate cells via induction of autophagy.

Hepatic stellate cells (HSCs) are major players in liver fibrogenesis. Accumulating evidence shows that suppression of autophagy plays an important role in the development and progression of liver disease. Phospholipase D1 (PLD1), which catalyzes the hydrolysis of phosphatidylcholine to yield phosphatidic acid (PA) and choline, was recently shown to modulate autophagy. However, little is known about the effects of PLD1 on the production of type I collagen that characterizes liver fibrosis. Here, we examined whether PLD1 regulates type I collagen levels in HSCs through induction of autophagy. Adenovirus-mediated overexpression of PLD-1 (Ad-PLD1) reduced type I collagen levels in the activated human HSC lines, hTERT and LX2. Overexpression of PLD1 in HSCs led to induction of autophagy as demonstrated by increased LC3-II conversion and formation of LC3 puncta, and decreased p62 abundance. Moreover, inhibiting the induction of autophagy by treating cells with bafilomycin or a small interfering (si)RNA for ATG7 rescued Ad-PLD1-induced suppression of type I collagen accumulation in HSCs. The effects of PLD on type I collagen levels were not related to TGF-ß/Smad signaling. Furthermore, treatment of cells with PA induced autophagy and inhibited type I collagen accumulation. The present study indicates that PLD1 plays a role in regulating type I collagen accumulation through induction of autophagy.

Factors predictive of perforation during endoscopic submucosal dissection for the treatment of colorectal tumors.

BACKGROUND AND AIM: Although perforation of the colon is known as one of the main complications of endoscopic submucosal dissection (ESD) for colorectal tumor management, factors predictive of perforation have not been fully evaluated. This study aimed to determine the factors associated with perforation during colorectal ESD. METHODS: Patients with colorectal tumors undergoing ESD were enrolled and their records were reviewed retrospectively. Age, sex, co-morbidity, medication history, procedure time, resection method, tumor size, location, gross morphology, the presence of fibrosis, and histologic findings were included as possible risk factors. In the cases where perforation had occurred, factors associated with the duration of hospitalization were analyzed. RESULTS: One hundred eight lesions in 108 patients were eligible for inclusion in the study (68 patients were male; mean patient age was 63.01 ± 10.71 years). Mean tumor size was 27.59 ± 10.10 mm (range: 8 - 53 mm). Laterally spreading tumor was the most common type (75 %), followed by the protruding type (25 %). Procedure time was 61.95 ± 41.90 minutes (range: 5 - 198 minutes). Complete en bloc resection was achieved for 85 lesions (78.7 %). Perforation occurred in 22 patients (20.4 %). Multivariate analysis confirmed that tumor size [odds ratio (OR): 1.084; 95 % confidence interval (CI): 1.015 - 1.158; P = 0.017] and the presence of fibrosis (OR: 4.551; 95 %CI: 1.092 - 18.960; P = 0.037) were independent risk factors for perforation. All cases of perforation were managed with nonsurgical treatment. Younger age and abdominal pain appeared to be related to prolonged hospitalization. CONCLUSION: Tumor size and fibrosis are important factors related to complications during colorectal ESD. Younger age and development of abdominal pain can predict the hospital course in patients with perforation after ESD.