AngRem104, an angiotensin II-induced novel upregulated gene in human mesangial cells, is potentially involved in the regulation of fibronectin expression.
Accumulation of extracellular matrix (ECM) in the glomerular mesangium is a common feature of many progressive renal diseases. Angiotensin II (AngII) plays important roles in the proliferation of glomerular mesangial cells (MC) as well as the synthesis of ECM such as fibronectin (FN) and collagens. However, the precise molecular signals responsible for these effects are unknown. To explore possible molecule mechanism of ECM accumulation related to AngII, suppression subtractive hybridization (SSH) was performed to screen and identify upregulated genes induced by AngII in cultured human MC. A novel gene, AngRem104 (GenBank accession number, AF367870), was isolated. The full-length cDNA of AngRem104 is 1690 bp, and it contains a 1041-bp open reading frame (ORF) encoding 347 amino acid residues with a predicted molecular mass of 37.2 kD. AngRem104 widely expressed in human heart, placenta, liver, muscle, kidney, and pancreas. Moreover, AngRem104 was found in human glomeruli and tubule by in situ hybridization. In human MC, the upregulation of AngRem104 induced by AngII was time-dependent, and it was dose-dependently blocked by AngII type 1 receptor antagonist (AT1RA), Losartan. The subcellular localization detected by AngRem104-pEGFP fusion protein revealed that AngRem104 was a nuclear protein. Interestingly, when AngRem104 was overexpressed by transfection of its sense construct, cDNA Microarray showed that two of the ECM-related genes, i.e., human mRNA for FN and integrin-beta-1 (FN receptor), dramatically upregulated their expressions. Furthermore, AngRem104 could regulate the expression of FN induced by AngII, which were detected by RT-PCR and quantitative real-time PCR, when AngRem104 was overexpressed. It is concluded that AngRem104 is a novel human gene potentially involved in the regulation of FN induced by AngII in human MC. These findings may provide new insights into mechanisms of glomerular sclerosis associated with AngII.
Liang
Xiubin
X
Renal Division of Peking University First Hospital, Institute of Nephrology, Peking University, Beijing, China.
Zhang
Hong
H
Zhou
Anyu
A
Wang
Haiyan
H
D000595:Amino Acid Sequence / Q000235:genetics; D000804:Angiotensin II / Q000494:pharmacology; D057911:Angiotensin Receptor Antagonists; D001483:Base Sequence / Q000235:genetics; D018076:DNA, Complementary / Q000235:genetics; D005353:Fibronectins / Q000235:genetics / Q000378:metabolism*; D005920:Glomerular Mesangium / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D007678:Kidney Glomerulus / Q000378:metabolism; D007684:Kidney Tubules / Q000378:metabolism; D019808:Losartan / Q000494:pharmacology; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000235:genetics / Q000502:physiology*; D012333:RNA, Messenger / Q000378:metabolism; D044140:Receptor, Angiotensin, Type 1; D014018:Tissue Distribution; D015854:Up-Regulation
D057911:Angiotensin Receptor Antagonists; D018076:DNA, Complementary; D005353:Fibronectins; D009687:Nuclear Proteins; D012333:RNA, Messenger; D044140:Receptor, Angiotensin, Type 1; D000804:Angiotensin II; D019808:Losartan