No abstract

Pigment epithelium-derived factor (PEDF) has been shown previously to prevent liver fibrosis and hepatic stellate cell (HSC) activation. By investigating the functional domains in PEDF, we identified a 34-mer peptide (residues Asp44-Asn77) that harbors the same function as the full-length PEDF protein. Not only did the 34-mer suppress the development of fibrosis in carbon tetrachloride (CCl4)-treated mouse liver but it also upregulated peroxisome proliferator-activated receptor-gamma (PPARγ) expression in HSCs in vivo. Platelet-derived growth factor (PDGF) plays a crucial role on the process of HSC activation in response to liver damage. The 34-mer suppressed PDGF-induced cell proliferation and expression of myofibroblastic marker proteins in primary rat HSC culture, increased the levels of PPARγ mRNA and protein in a dose-dependent manner and markedly reduced the level of active β-catenin protein, an HSC activating factor, in HSC-T6 cells. Similarly, IWR-1, an inhibitor of the Wnt response, displayed the same effect as the 34-mer in preventing HSC-T6 activation. The Wnt signaling-mediated PPARγ suppression was abolished by both the IWR-1 inhibitor and a small interfering RNA (siRNA) targeting β-catenin and the Wnt coreceptor, LRP6. Both PEDF and the 34-mer down-regulated PDGF receptor-α/β expression and blocked the PDGF-induced phosphorylation of Akt and ERK. Moreover, the inhibitory effect on PDGF receptor expression was abolished by PPARγ antagonists and PPARγ siRNA. Our observations indicate that the PEDF-derived 34-mer peptide can mimic PEDF in attenuating HSC activation. Investigation of this 34-mer peptide led to the identification of a signaling mechanism involving PPARγ induction, suppression of Wnt/β-catenin signaling and down-regulation of the PDGF receptor-α/β.

No abstract

There are conflicting reports on cancer risk associated with angiotensin-converting enzyme (ACE) inhibitors/angiotensin receptor blockers (ARBs). This retrospective cohort study was conducted to analyze the risk of cancer development in patients who received ACE inhibitors/ARBs as treatment for essential hypertension. Using the Taiwan National Health Insurance Research Database, 297,688 eligible study patients with essential hypertension were identified. According to their antihypertensive prescriptions, the study patients were stratified into an ACE inhibitor group, an ARB group, or a control group. After matching, participants were observed for the occurrence of cancer. In the ACE inhibitor group compared with the control group, the hazard ratio was 0.51 (95% confidence interval, 0.39-0.68). In the ARB group compared with the control group, the hazard ratio was 0.8 (95% confidence interval, 0.65-0.97). Regular use of ACE inhibitors/ARBs was not associated with an increased risk of cancer development and was actually found to decrease overall cancer risk in this study. J Clin Hypertens (Greenwich). 2014;16:27-33. ª2013 Wiley Periodicals, Inc.

BackgroundAssociation between nonalcoholic fatty liver disease (NAFLD) and future psoriasis has not yet been confirmed, although the two diseases partially share a common pathogenesis pathway. Studies have revealed an association between psoriasis and subsequent NAFLD; however, these studies were limited to small sample sizes and a cross-sectional study design. Hence, the main objective of this population-based longitudinal cohort study was to evaluate the bidirectional association between psoriasis and NAFLD.MethodsData were retrieved from Taiwan’s National Health Insurance Research Database. Patients with new-onset NAFLD and psoriasis were respectively enrolled in two cohorts. For each comparison cohort, propensity-score-matched controls with no record of NAFLD or psoriasis were selected. An adjusted hazard ratio (aHR) was applied to evaluate subsequent risks.ResultsThe risk of patients with new-onset NAFLD developing psoriasis was statistically significant, with an HR of 1.07 (95% CI, 1.01–1.14). For younger patients with NAFLD, the risk of developing psoriasis was 1.3-fold higher. The risk of patients with new-onset psoriasis developing NAFLD in the future was 1.28-fold higher than that of patients without psoriasis (95% CI, 1.21–1.35), and patients in younger psoriasis subgroups below the age of 40 years were at a higher risk than those in older subgroups, with an aHR of 1.55 (95% CI, 1.40–1.71).ConclusionEvidence supports a bidirectional association between NAFLD and psoriasis, especially in patients below the age of 40 years. The correlation between the two diseases and the subsequent risk of disease development should be considered when caring for patients.