HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: 293/4/F1381    most recent 00185.2007v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Web of Science (7) Citing Articles via Google Scholar Google Scholar Articles by Graham, S. Articles by Ma, R. Search for Related Content PubMed PubMed Citation Articles by Graham, S. Articles by Ma, R.

Downregulation of TRPC6 protein expression by high glucose, a possible mechanism for the impaired Ca²⁺ signaling in glomerular mesangial cells in diabetes

¹Department of Integrative Physiology, ²Department of Pharmacology and Neuroscience, University of North Texas Health Science Center at Fort Worth, Fort Worth, Texas; ³Department of Physiology, Anhui Medical University, Hefei, People's Republic of China; and ⁴Department of Medicine, Department of Cell Biology, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma

Submitted 17 April 2007 ; accepted in final form 10 August 2007

The present study was performed to investigate whether transient receptor potential (TRPC)6 participated in Ca²⁺ signaling of glomerular mesangial cells (MCs) and expression of this protein was altered in diabetes. Western blots and real-time PCR were used to evaluate the expression level of TRPC6 protein and mRNA, respectively. Cell-attached patch-clamp and fura-2 fluorescence measurements were utilized to assess angiotensin II (ANG II)-stimulated membrane currents and Ca²⁺ responses in MCs. In cultured human MCs, high glucose significantly reduced expression of TRPC6 protein, but there was no effect on either TRPC1 or TRPC3. The high glucose-induced effect on TRPC6 was time and dose dependent with the maximum effect observed on day 7 and at 30 mM glucose, respectively. In glomeruli isolated from streptozotocin-induced diabetic rats, TRPC6, but not TRPC1, was markedly reduced compared with the glomeruli of control rats. Furthermore, TRPC6 mRNA in MCs was also significantly decreased by high glucose as early as 1 day after treatment with maximal reduction on day 4. Patch-clamp experiments showed that ANG II-stimulated membrane currents in MCs were significantly attenuated or enhanced by knockdown or overexpression of TRPC6, respectively. Fura-2 fluorescence measurements revealed that the ANG II-induced Ca²⁺ influxes were markedly inhibited in MCs with TRPC6 knockdown, reminiscent of the impaired Ca²⁺ entry in response to ANG II in high glucose-treated MCs. These results suggest that the TRPC6 protein expression in MCs was downregulated by high glucose and the deficiency of TRPC6 protein might contribute to the impaired Ca²⁺ signaling of MCs seen in diabetes.

Ca²⁺ influxes; glomeruli; diabetic nephropathy; hyperfiltration

This article has been cited by other articles:

				S. Sours-Brothers, M. Ding, S. Graham, and R. Ma Interaction Between TRPC1/TRPC4 Assembly and STIM1 Contributes to Store-Operated Ca2+ Entry in Mesangial Cells Experimental Biology and Medicine, June 1, 2009; 234(6): 673 - 682. [Abstract] [Full Text] [PDF]

				J. Abramowitz and L. Birnbaumer Physiology and pathophysiology of canonical transient receptor potential channels FASEB J, February 1, 2009; 23(2): 297 - 328. [Abstract] [Full Text] [PDF]

				J. Du, M. Ding, S. Sours-Brothers, S. Graham, and R. Ma Mediation of angiotensin II-induced Ca2+ signaling by polycystin 2 in glomerular mesangial cells Am J Physiol Renal Physiol, April 1, 2008; 294(4): F909 - F918. [Abstract] [Full Text] [PDF]