Involvement of F-Actin in Chaperonin-Containing t-Complex 1 Beta Regulating Mouse Mesangial Cell Functions in a Glucose-Induction Cell Model

Jin-Shuen Chen,Yuh-Feng Lin,Lai-King Yeung,Li-Chien Chang,Chia-Chao Wu

doi:10.1155/2011/565647

Abstract

The aim of this study is to investigate the role of chaperonin-containing t-complex polypeptide 1 beta (CCT2) in the regulation of mouse mesangial cell (mMC) contraction, proliferation, and migration with filamentous/globular-(F/G-) actin ratio under high glucose induction. A low CCT2 mMC model induced by treatment of small interference RNA was established. Groups with and without low CCT2 induction examined in normal and high (H) glucose conditions revealed the following major results: (1) low CCT2 or H glucose showed the ability to attenuate F/G-actin ratio; (2) groups with low F/G-actin ratio all showed less cell contraction; (3) suppression of CCT2 may reduce the proliferation and migration which were originally induced by H glucose. In conclusion, CCT2 can be used as a specific regulator for mMC contraction, proliferation, and migration affected by glucose, which mechanism may involve the alteration of F-actin, particularly for cell contraction.

Highlights

Functions of mesangial cell contraction, migration, and proliferation have been reported to be correlated with the development of diabetic nephropathy (DN)
As our previous study found mouse mesangial cells incubating with high glucose has the upregulation of CCT2, the prime work of this study is to find the optimal amount of small interfering RNA (siRNA) to establish a low CCT2 model
Our findings suggest that mouse mesangial cell (mMC) treated by H glucose or CCT2siRNA both showed a similar effect on the attenuating of PMA-stimulated contraction, and there was no synergetic effect for H glucose plus CCT2siRNA

Summary

Introduction

Functions of mesangial cell contraction, migration, and proliferation have been reported to be correlated with the development of diabetic nephropathy (DN). Mesangial cell contraction regulating intraglomerular pressure contributes to the occurrence of glomerular hyperfiltration in early DN and progresses to end-stage renal disease (ESRD) [1]. Alteration in mesangial cell migration may limit repair following mesangiolysis and thereby contribute to the loss of kidney function in diabetic nephropathy [2, 3]. As the integrity of cytoskeletons is changed during mesangial cell contraction, migration, and proliferation, actin, the most important cytoskeletal protein, should play a role in the development of DN [5]. The chaperonin family may play an important role in maintaining the normal function of actin as the function of chaperone-assisted protein folding in cell allows many cytosolic proteins to attain the correct folded states and functional conformations during protein synthesis or during recovery from their denatured states [7]

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