Albumin overload down-regulates integrin-beta 1 through reactive oxygen species-endoplasmic reticulum stress pathway in podocytes

作者：Cheng Yu Chi; Chenz Chien An^*; Chang Jer Ming; Chent Hung Chun

来源：Journal of Biochemistry, 2015, 158(2): 101-108.

DOI：10.1093/jb/mvv020

• endoplasmic reticulum stress
• glomerular nephropathy
• integrin
• podocyte
• proteinuria

Proteinuria is a major hallmark of glomerular nephropathy and endoplasmic reticulum (ER) stress plays an important role in glomerular nephropathy. The protein levels of integrin-beta 1 in podocytes are found to be negative correlation with amount of proteinuria. This study investigated whether urinary protein, particularly albumin, induced ER stress that consequently reduced integrin-beta 1 expression. All experiments were performed using primary cultured rat podocyte. Protein and mRNA expression were measured by western blotting and semiquantified reverse transcriptase polymerase chain reaction. Albumin uptake was found at 1 h after albumin addition. Albumin reduced precursor and mature forms of integrin-beta 1, but did not change mRNA levels of integrin-beta 1. Albumin induced reactive oxygen species (ROS) generation and ER stress. Antioxidant (N-acetylcysteine) suppressed albumin-induced ER stress and decrements in precursor and mature forms of integrin-beta 1. Then, ER stress inhibitors (4-phenylbutyrate and salubrinal) also inhibited albumin-induced decrements in precursor and mature forms of integrin-beta 1. The potent ER stress inducers (thapsigargin and tunicamycin) directly decreased precursor and mature forms of integrin-beta 1 and led appearance of unglycosylated core protein of integrin-beta 1. Our results show that in proteinuric disease, albumin decreases precursor and mature forms of integrin-beta 1 through ROS-ER stress pathway in podocytes.

• 出版日期2015-8
• 单位河北医科大学