Cardiac fibroblasts (CFs) are the primary cell type responsible for cardiac fibrosis during pathological myocardial remodeling. Several studies have illustrated that pirfenidone (5-methyl-1-phenyl-2-[1H]-pyridone) attenuates cardiac fibrosis in different animal models. However, the effects of pirfenidone on cardiac fibroblast behavior have not been examined. In this study, we investigated whether pirfenidone directly modulates cardiac fibroblast behavior that is important in myocardial remodeling such as proliferation, myofibroblast differentiation, migration and cytokine secretion. Fibroblasts were isolated from neonatal rat hearts and bioassays were performed to determine the effects of pirfenidone on fibroblast function. We demonstrated that treatment of CFs with pirfenidone resulted in decreased proliferation, and attenuated fibroblast α-smooth muscle actin expression and collagen contractility. Boyden chamber assay illustrated that pirfenidone inhibited fibroblast migration ability, probably by decreasing the ratio of matrix metalloproteinase-9 to tissue inhibitor of metalloproteinase-1. Furthermore, pirfenidone attenuated the synthesis and secretion of transforming growth factor-β1 but elevated that of interleukin-10. These direct and pleiotropic effects of pirfenidone on cardiac fibroblasts point to its potential use in the treatment of adverse myocardial remodeling.

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a b s t r a c tIt is well known that there are huge land use and land cover changes (LUCC) all over the world in recent decades, and plenty of ensuing effect appeared on the energy and water balance. This study aims to analyze the impacts of land use and land cover changes on the energy and water balance in the Heihe River Basin of China during 2000-2010, and four key study sites with representative hydrological stations and dramatic LUCC in the past decades were selected to illustrate the responses of the energy and water balance to LUCC. First, LUCC of the Heihe River Basin from 2000 to 2010 was analyzed based on the interpretation of remote sensing images. Then a series of indicators of the energy and water balances were simulated with the Weather Research and Forecasting (WRF) model and corresponding land use and land cover data. Thereafter the impacts of LUCC on the surface energy and water balance were detected and analyzed. The spatial-temporal variance of the impacts of LUCC on energy and water balance in a typical arid inland river basin was specifically presented in following analysis. The results show that different land use/cover conversions result in various energy balances. During this process, the most significant impacts on surface energy balance occurred when grassland was converted to barren or sparsely vegetated land. As for water balance, the impact is measured with variations of precipitation, runoff and evapotranspiration induced by LUCC, which were also remarkable, although seasonal trends of the effects are similar among various land use/cover conversions during 2000-2010. At last, policy suggestions, e.g., shifting the water balance by LUCC to improve the water management, are given to conclude this study.