Abstract
In vitro and animal studies continue to elucidate the mechanisms of fibrosis and have led to advancements in treatment for idiopathic pulmonary fibrosis and cirrhosis, but the search for treatments for renal fibrosis has been more disappointing. Here, we will discuss homeodomain-interacting-protein kinase 2 (HIPK2), a novel regulator of fibrosis that acts upstream of major fibrosis signaling pathways. Its key role in renal fibrosis has been validated in vitro and in several murine models of chronic kidney diseases (CKD).
Highlights
Fibrosis and end stage renal disease (ESRD)Fibrosis is the final common pathway for chronic kidney diseases (CKD)
One potential reason is that renal fibrosis is mediated by a complex signaling network of several different pathways
homeodomain-interacting-protein kinase 2 (HIPK2) has been identified as a master regulator of kidney fibrosis and acts upstream of several major fibrosis-signaling pathways
Summary
Fibrosis is the final common pathway for chronic kidney diseases (CKD). Renal fibrosis occurs as an overwhelming response to tissue injury. The attempt to repair damage begins with the recruitment of inflammatory cells, but ends with an unchecked inflammatory response that activates matrixproducing cells leading to tubular cell apoptosis, irreversible scarring, loss of renal function, and end stage renal disease (ESRD) (Chuang et al, 2012). CKD and ESRD are major public health problems with increasing prevalence worldwide and are associated with early mortality, poor quality of life, and high healthcare costs. At present, there are no effective therapies to prevent or slow the progression of renal fibrosis, and the treatment options for patients with ESRD are limited to dialysis and renal transplant. To develop effective molecular targets for prevention and treatment of renal fibrosis, it is important to gain a better understanding of the mechanisms involved. We will review major signaling pathways that contribute to aberrant wound healing and fibrosis with a focus on homeodomain-interacting-protein kinase 2 (HIPK2) which acts upstream of several pro-fibrosis pathways
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