TRPC channels: Regulation, dysregulation and contributions to chronic kidney disease

TRPC6 inactivation does not protect against diabetic kidney disease in streptozotocin (STZ)‐treated Sprague‐Dawley rats

“…Diabetic nephropathy (DN)() is a major cause of end‐stage renal disease (ESRD) . Current therapies for DN entail intensive glycemic control and inhibition of renin‐angiotensin systems, but in many cases, these therapies fail to prevent progression to ESRD .…”

“…Canonical transient receptor potential‐6 channels are non‐selective Ca 2+ ‐permeable cation channels expressed in many different cell types. We have recently reviewed the current understanding of the role of TRPC6 and related cationic channels in the pathophysiology of kidney disease, and their status as potential therapeutic targets . Podocyte TRPC6 channels are expressed at the slit diaphragm domains of foot processes and along major processes and in the cell body .…”

“…We have recently reviewed the current understanding of the role of TRPC6 and related cationic channels in the pathophysiology of kidney disease, and their status as potential therapeutic targets . Podocyte TRPC6 channels are expressed at the slit diaphragm domains of foot processes and along major processes and in the cell body . They are also present in mesangial cells .…”

“…Gain‐of‐function mutations in the Trpc6 gene are associated with familial forms of focal segmental glomerulosclerosis (FSGS) . TRPC6 dysregulation is also linked to progression of acquired forms of proteinuric kidney diseases . We have recently reported that podocyte TRPC6 channels are dysregulated in the chronic puromycin aminonucleoside (PAN) nephrosis model of acquired FSGS in Sprague‐Dawley rats, as well as in response to circulating factors implicated in primary and recurrent FSGS .…”

“…It has been widely reported that glomerular TRPC6 channels are substantially more abundant in type 1 and type 2 diabetes and in podocytes cultured in the presence of elevated external glucose . This is due at least in part to oxidative stress that can be driven by hyperglycemia, and by the surrounding pro‐inflammatory milieu . In addition, a protective effect of Trpc6 knockout has been reported in animal models of type 1 diabetes, although the outcomes varied substantially depending on which animal model was used.…”