PGE2 induces apoptosis of hepatic stellate cells and attenuates liver fibrosis in mice by downregulating miR-23a-5p and miR-28a-5p.

MicroRNAs (miRNAs), small noncoding RNAs modulating messenger RNA (mRNA) and protein expression, have emerged as key regulatory molecules in chronic liver diseases, whose end stage is hepatic fibrosis, a major global health burden. Pharmacological strategies for prevention or treatment of hepatic fibrosis are still limited, what makes it necessary to establish a better understanding of the molecular mechanisms underlying its pathogenesis. In this context, we have recently shown that cyclooxygenase-2 (COX-2) expression in hepatocytes restricts activation of hepatic stellate cells (HSCs), a pivotal event in the initiation and progression of hepatic fibrosis. Here, we evaluated the role of COX-2 in the regulation of a specific set of miRNAs on a mouse model of CCl4 and bile duct ligation (BDL)-induced liver fibrosis. Our results provide evidence that COX-2 represses miR-23a-5p and miR-28-5p expression in HSC. The decrease of miR-23a-5p and miR-28-5p expression promotes protection against fibrosis by decreasing the levels of pro-fibrogenic markers α-SMA and COL1A1 and increasing apoptosis of HSC. Moreover, we demonstrate that serum levels of miR-28-5p are decreased in patients with chronic liver disease. These results suggest a protective effect exerted by COX-2-derived prostanoids in the process of hepatofibrogenesis.

[Study of the use of antiulcer and hypolipemic drugs in the Primary Care District of Jerez (Cádiz)]. / Estudio de utilización de antiulcerosos e hipolipemiantes en el Distrito de Atención Primaria de Jerez (Cádiz).

OBJECTIVES: To identify the prescription profile for anti-ulcerous and hypolipemic drugs during the three-year period 1994-1996 in the Jerez Primary Care district, and the differences in prescription between the reformed (Health Centres) and the unreformed networks (non-hospital clinics). DESIGN: Longitudinal, retrospective study, out of a complete sample. SETTING: Primary Care. PARTICIPANTS: Total number of general medical consultations. MEASUREMENTS AND MAIN RESULTS: The first quarter of each year was studied. Dose per 1,000 inhabitants per day (DID) was the indicator. Consumption of anti-ulcer drugs grew from 11.43 DID in 1994 to 15 in 1996 (31.23%). In the reformed network, consumption grew from 10.25 to 13.26 DID (29.37%); and in the non-reformed, from 12.56 to 16.72 DID (33.12%). Hypolipemic use went up from 8 DID in 1994 to 10.32 in 1996 (29%). CONCLUSIONS: Anti-ulcer and hypolipemic drug use increased over the study period. Both consumption and increases were lower in Health Centres. Increase in statin use led to a light decline in fibrate use in the reformed network, but not in non-hospital clinics.