title: Carboxy-terminal modulator protein attenuated extracellular matrix deposit by inhibiting phospho-Akt, TGF-β1 and α-SMA in kidneys of diabetic mice.
abstract: Glomerulosclerosis and tubular interstitial extracellular matrix deposit and fibrosis are the main features of diabetic nephropathy, which are mediated by activation of PI3K/Akt signal pathway. Carboxy-terminal modulator protein (CTMP) is known as a negative regulator of PI3K/Akt pathway. Whether CTMP regulates renal extracellular matrix metabolism of diabetic nephropathy is still not known. Here, renal decreased CTMP, enhanced phospho-Akt (Ser 473), TGF-β1, α-SMA and extracellular matrix deposit are found in diabetic mice. Furthermore, high glucose decreases CTMP expression accompanied by enhanced phospho-Akt (Ser 473), TGF-β1 and α-SMA in cultured human renal proximal tubular epithelial cells (HKC), which are effectively prevented by transfection of pYr-ads-4-musCTMP vector. Moreover, delivery of pYr-ads-4-musCTMP vector into kidneys via tail vein of diabetic mice increases CTMP expression by 8.84 times followed by 60.00%, 76.50% and 24.37% decreases of phospho-Akt (Ser 473), TGF-β1 and α-SMA compared with diabetic mice receiving pYr-adshuttle-4 vector. Again, increased renal extracellular matrix accumulation of diabetic mice is also inhibited with delivery of pYr-ads-4-musCTMP vector. Our results indicate that CTMP attenuates renal extracellular matrix deposit by regulating the phosphorylation of Akt, TGF-β1 and α-SMA expression in diabetic mice.
authors.affiliation: Department of Pathology, Hebei Medical University, NO. 361. Zhongshan East Road, Shijiazhuang, Hebei, China.
authors.forename: Ning
authors.initials: N
authors.lastname: Chen
authors.affiliation: Department of Pathology, Hebei Medical University, NO. 361. Zhongshan East Road, Shijiazhuang, Hebei, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Hao
authors.affiliation: Department of Pathology, Hebei Medical University, NO. 361. Zhongshan East Road, Shijiazhuang, Hebei, China.
authors.forename: Lisha
authors.initials: L
authors.lastname: Li
authors.affiliation: Department of Pathology, Hebei Medical University, NO. 361. Zhongshan East Road, Shijiazhuang, Hebei, China.
authors.forename: Fan
authors.initials: F
authors.lastname: Li
authors.affiliation: Department of Pathology, Hebei Medical University, NO. 361. Zhongshan East Road, Shijiazhuang, Hebei, China.
authors.forename: Shuxia
authors.initials: S
authors.lastname: Liu
authors.affiliation: Department of Pathology, Hebei Medical University, NO. 361. Zhongshan East Road, Shijiazhuang, Hebei, China. Electronic address: duanhuijun@hotmail.com.
authors.forename: Huijun
authors.initials: H
authors.lastname: Duan
mesh_terms: D000199:Actins / Q000378:metabolism; D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism*; D003928:Diabetic Nephropathies / Q000378:metabolism*; D005109:Extracellular Matrix / Q000378:metabolism* / Q000473:pathology; D007668:Kidney / Q000378:metabolism* / Q000473:pathology; D008297:Male; D051379:Mice; D010170:Palmitoyl-CoA Hydrolase; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D053773:Transforming Growth Factor beta1 / Q000378:metabolism*
chemical_list: D000199:Actins; D002352:Carrier Proteins; D053773:Transforming Growth Factor beta1; C544013:alpha-smooth muscle actin, mouse; D051057:Proto-Oncogene Proteins c-akt; C527670:CTMP protein, mouse; D010170:Palmitoyl-CoA Hydrolase
keywords: Carboxy-terminal modulator protein; Diabetic nephropathy; PI3K/Akt; TGF-β1; α-SMA