Abstract
ABSTRACTCaffeine has been demonstrated to possess anti-fibrotic activity against liver fibrosis. However, its role in renal fibrosis remained unclear. This study investigated the effects of caffeine on renal fibroblast activation induced by hypoxia (one of the inducers for renal fibrosis). BHK-21 fibroblasts were cultured under normoxia or hypoxia with or without caffeine treatment. Hypoxia increased levels of fibronectin, α-smooth muscle actin, actin stress fibers, intracellular reactive oxygen species (ROS), and oxidized proteins. However, caffeine successfully preserved all these activated fibroblast markers to their basal levels. Cellular catalase activity was dropped under hypoxic condition but could be reactivated by caffeine. Hif1a gene and stress-responsive Nrf2 signaling molecule were elevated/activated by hypoxia, but only Nrf2 could be partially recovered by caffeine. These data suggest that caffeine exhibits anti-fibrotic effect against hypoxia-induced renal fibroblast activation through its antioxidant property to eliminate intracellular ROS, at least in part, via downstream catalase and Nrf2 mechanisms.
Highlights
Chronic kidney disease (CKD) is still a major health concern worldwide
This study investigated the effects of caffeine on renal fibroblast activation induced by hypoxia
Fibroblasts are differentiated into their active phenotype, which have been defined by an increase of α-smooth muscle actin (α-SMA) and accumulation of the excessive amount of extracellular matrix (ECM) constituents [4]
Summary
Chronic kidney disease (CKD) is still a major health concern worldwide. It is well known that hypertension and diabetes mellitus are the major etiologies of CKD, which is histopathologically characterized by interstitial inflammation, tubular atrophy, and fibrosis [1]. Renal fibrosis has been considered as an aberration of wound/ tissue healing process, in which there is a progression rather than improvement of scar formation after renal tissue injury, and fibroblasts play a crucial role in this phenomenon [2]. Fibroblasts are quiescent cells residing in the renal interstitium that sustain renal tissue structure [3]. They are the major cells responsible for synthesis and turnover of extracellular matrix (ECM) during normal development and adaptive homeostasis after cell/tissue injury [3]. Fibroblasts are differentiated into their active phenotype (known as myofibroblasts), which have been defined by an increase of α-smooth muscle actin (α-SMA) and accumulation of the excessive amount of ECM constituents [4]. Actin filaments turn into stress fiber bundles during the fibroblast activation [2]
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