title: The novel role of TRPC6 in vitamin D ameliorating podocyte injury in STZ-induced diabetic rats.
abstract: Podocyte injury plays a critical role in the development and progression of diabetic nephropathy (DN). Over expression of TRPC6 on the podocytes has been revealed to cause podocyte injury in non-diabetic states. Besides, the emerging evidence from clinic revealed that vitamin D could reduce albuminuria and improve renal function, which was associated with podocyte protection. Our study aimed to investigate whether calcitriol ameliorating podocyte impairment is associated with regulation of the expression of TRPC6 in STZ-induced rats. Sprague-Dawley rats were randomly divided into three groups: normal control, DN, and DN treated with calcitriol (DN + VD); VD rats were treated with 0.1 μg/kg/d calcitriol by gavage. DN model rats were established by intraperitoneal injections of streptozocin. The rats were sacrificed after 18 weeks treatment. DN rats exhibited increased proteinuria accompanied by elevated TRPC6 expression. Treatment with calcitriol not only reduced proteinuria, but also normalized TRPC6 expression. Meanwhile, in DN rats, the expression of podocyte specific markers including nephrin and podocin was significantly decreased, accompanied by increased desmin, a marker of podocyte injury. Treatment with calcitriol reversed above changes. In addition, vitamin D receptor (VDR) was significantly decreased, whereas this reduction was attenuated by the calcitriol treatment. Moreover, TRPC6 was positively correlated with both 24 h urinary protein and desmin. In contrast, TRPC6 was negatively correlated with both VDR and nephrin expression in podocytes. Calcitriol can ameliorate podocyte injury, which is contributed by the inhibition of enhanced TRPC6 expression in the early stages of DN rats.
authors.affiliation: Institute of Nephrology, Zhong Da Hospital, Southeast University School of Medicine, Nanjing, 210009, Jiangsu, China, tonyxlz@163.com.
authors.forename: Xiaoliang
authors.initials: X
authors.lastname: Zhang
authors.forename: Zhixia
authors.initials: Z
authors.lastname: Song
authors.forename: Yinfeng
authors.initials: Y
authors.lastname: Guo
authors.forename: Min
authors.initials: M
authors.lastname: Zhou
mesh_terms: D000419:Albuminuria / Q000378:metabolism; D000818:Animals; D002117:Calcitriol / Q000494:pharmacology* / Q000627:therapeutic use; D003893:Desmin / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000150:complications / Q000188:drug therapy / Q000378:metabolism*; D003928:Diabetic Nephropathies / Q000188:drug therapy / Q000378:metabolism*; D007668:Kidney / Q000187:drug effects / Q000473:pathology; D008297:Male; D050199:Podocytes / Q000187:drug effects / Q000378:metabolism*; D017207:Rats, Sprague-Dawley; D018167:Receptors, Calcitriol / Q000378:metabolism; D013311:Streptozocin; D050052:TRPC Cation Channels / Q000502:physiology*; D025721:WT1 Proteins / Q000378:metabolism
chemical_list: D003893:Desmin; D018167:Receptors, Calcitriol; D050052:TRPC Cation Channels; C492145:Trpc6 protein, rat; D025721:WT1 Proteins; D013311:Streptozocin; D002117:Calcitriol