Ang II enhances tubular cell Ets-1 expression and associated down stream signaling is mediated through AT1 receptors.
Angiotensin II (Ang II) has been reported to play an important role in both the development and progression of renal injury. Many of the downstream effects of Ang II are mediated through the activation of nuclear factor-kappaB (NF-kappaB). In the present study, we evaluated the effect of Ang II on the activation of Ets-1 (a transcription factor) in tubular cells. In addition, we studied the expression of pro-inflammatory molecules transcribed by Ets-1 in response to Ang II. Mice receiving Ang II infusion showed enhanced renal cortical mRNA expression of Ets-1. Immunolabeling studies localized the expression of Ets-1 in distal tubular cells of mice receiving Ang II. However, this effect of Ang II was mitigated by telmisartan, an AT1-receptor blocker. Mice receiving Ang II infusion also showed increased tubular cell expression of macrophage chemoattractant protein-1 (MCP-1), plasminogen activator inhibitor-1 (PAI-1), and p21 when compared with control mice; nevertheless, this effect of Ang II was attenuated by telmisartan. In in vitro studies, Ang II enhanced mRNA expression of Ets-1 by MDCK cells. However, this effect of Ang II was inhibited by losartan, an AT1-receptor blocker. Losartan also inhibited Ang II-induced PAI-1 and p21 expression by MDCK cells. These findings indicate that Ang II-induced tubular cell expression Ets-1 and associated downstream signaling is mediated through AT1 receptors.
Kumar
Dileep
D
Department of Medicine, North Shore-LIJ Health System, Great Neck, New York 11021, USA.
Luan
Liming
L
Pathak
Shresh
S
Salhan
Divya
D
Magoon
Sandeep
S
Singhal
Pravin C
PC
D000804:Angiotensin II / Q000494:pharmacology*; D057911:Angiotensin Receptor Antagonists / Q000494:pharmacology; D000818:Animals; D018929:Cell Culture Techniques; D007687:Kidney Tubules, Proximal / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D050784:Proto-Oncogene Protein c-ets-1 / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D044140:Receptor, Angiotensin, Type 1 / Q000187:drug effects*; D015398:Signal Transduction / Q000187:drug effects*; D014662:Vasoconstrictor Agents / Q000494:pharmacology*
D057911:Angiotensin Receptor Antagonists; D050784:Proto-Oncogene Protein c-ets-1; D012333:RNA, Messenger; D044140:Receptor, Angiotensin, Type 1; D014662:Vasoconstrictor Agents; D000804:Angiotensin II