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Cisplatin (cis-diamminedichloroplatinum(II)) is an effective chemotherapeutic agent, and is successfully used in the treatment of a wide range of tumors. Despite its effectiveness as an anti-tumor drug, nephrotoxic side effects have significantly restricted its clinical use. Tubular epithelial cell deletion following cisplatin treatment is a major cause of renal injury. Oxidative stress significantly contributes to cisplatin-associated cytotoxicity, and use of antioxidants could counteract such cytotoxic effects of cisplatin. The renal microenvironmental changes following cisplatin treatment is a complex process and could be broadly categorized into three main pathological events, which at times might overlap: initial cytotoxic events, inflammatory events and fibroproliferative events. Stress responses and heat shock proteins generated following cisplatin treatment are actively involved in the initiation and progression of these events. In this article, we will briefly summarize factors involved in various phases of cisplatin-induced renal injuries.

Heat shock proteins (HSPs) are a distinctive class of proteins that have evolved to cope with stress to provide cellular defence against a wide range of cell injuries. HSPs play an important role in the assembly and folding of intracellular polypeptides, and help in restoring the biological activities of abnormal proteins. Cellular stress responses include a transient rearrangement of functional activities, in order to protect and maintain essential cellular functions, possibly by inducing HSPs. HSPs help in restoring protein homeostasis and assist in cellular recovery from stress, either by repairing damaged proteins through refolding or by degrading them. Recent studies have documented the important roles of stress proteins in renal cell survival and matrix remodeling in a number of acute and chronic renal diseases. This brief review summarizes some of the important aspects of HSPs and their relevance to various renal diseases.

Despite recent progress in identifying a number of important factors that may play central roles in various renal diseases, the precise molecular basis of renal injuries remains unclear. Recent studies have documented an important role for oxidant stress in several renal diseases. Oxidant stress by overproduction of reactive oxygen species, generation of reactive nitrogen species, and/or modulation of cellular antioxidant enzyme activities, resulting in the activation of certain transcription factors, and synthesis and/or release of inflammatory cytokines, chemokines, growth factors, and extracellular matrix proteins. These changes alter the balance in the microenvironment of the kidney, and may activate signaling cascades that induce and propagate renal injury. Complex molecular interactions and cross-talk between the activated signaling pathways, in turn, define the nature and clinical course of the disease process. In this article, we will briefly present the relevance of the oxidant stress in the pathogenesis of various renal diseases.

Recent research has greatly increased our knowledge regarding the molecular mechanisms of collagen synthesis and processing. Heat specific shock protein (HSP47) is a collagenspecific molecular chaperone, and helps in post-translational modifications of procollagens, during biosynthesis of collagen. Both in vivo and in vitro studies have convincingly demonstrated that HSP47 is localized in the endoplasmic reticulum of collagen-producing cells, and that its synthesis is closely associated with the rate of procollagen assembly. Recent studies are directed towards the pathological relevance of HSP47 in tissue scarring, a process that is characterized by excessive accumulation of collagens. It appears likely that increased levels of HSP47 in fibrotic diseases assist in increased assembly of procollagen, and thereby help in excessive accumulation of collagens in the fibrotic mass. Such profibrotic effects of HSP47 suggest that modulation of HSP47 expression in scarring diseases might alter the course of fibrotic diseases. In this brief article, we review the role of HSP47 in renal fibrotic diseases and its relevance to other scarring diseases.