Effect of Losartan on the mRNA Expressions of MT3-MMP and TIMP-2 in Diabetic Kidneys

Ding, Huanyu; Xu, Mingqing; Guo, Ying; Chen, Li-Long; Zhang, Shaoling; Li, Feng; Fu, Zhen-Yan

doi:10.1900/rds.2005.2.216

Cited by 6 publications

(5 citation statements)

References 14 publications

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“…33–35 However, the MMP/TIMP ratio, in the case of MMP-2/TIMP-2, has been reported to be markedly decreased by ANG II and increased by losartan. 36…”

Section: Discussionmentioning

confidence: 99%

Physiological regulation of MMPs and tPA/PAI in the arterial wall of rats by noradrenergic tone and angiotensin II

Dab

Hachani

Dhaouadi

et al. 2011

J Renin Angiotensin Aldosterone Syst

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The interactions between the sympathetic nervous system (SNS) and angiotensin II (ANG II), and their direct effects in vitro on the enzymes involved in vascular extracellular matrix (ECM) degradation, were examined. Rats were treated with guanethidine, losartan or the combined treatments. mRNA, protein and activity of matrix metalloproteinase (MMP)-2 and MMP-9 and mRNA of tissue plasminogen activator (t-PA) and plasminogen activator inhibitor 1 (PAI-1) were quantified in abdominal aorta (AA) and femoral artery (FA). Norepinephrine (NE) or ANG II with adrenergic (β, α1 and α2) or losartan antagonists was tested for MMP mRNA response in cultured vascular smooth muscle cells (VSMCs). Combined treatment enhances the inhibition of MMP-2 mRNA and protein level induced by simple treatment in AA. However MMP-9 in AA and MMP mRNA in FA were reduced in the same order by treatments. MMP activities were not affected by treatments. The t-PA/PAI-1 ratio, which reflects the fibrinolytic balance, remained higher after treatments. In cultured VSMCs, NE induced stimulation of MMP mRNA via α2 and β adrenergic receptors and MMP-2 activity via β adrenergic receptors, while ANG II-induced stimulation was abrogated by losartan. Overall, there is a synergic inhibition of both systems on the level of MMP-2 in AA.

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“…33–35 However, the MMP/TIMP ratio, in the case of MMP-2/TIMP-2, has been reported to be markedly decreased by ANG II and increased by losartan. 36…”

Section: Discussionmentioning

confidence: 99%

Physiological regulation of MMPs and tPA/PAI in the arterial wall of rats by noradrenergic tone and angiotensin II

Dab

Hachani

Dhaouadi

et al. 2011

J Renin Angiotensin Aldosterone Syst

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“…Accordingly, we found that none of the aforementioned factors were associated with changes in mRNA expression of PAFR in PBMCs during the follow-up period. However, changes in mRNA expression of PAFR in PBMCs were associated with the changes in mRNA expressions of other genes, namely CD36 [25,26], IP10 [27], and TIMP2 [28,29] in PBMCs. These genes, as well as PAFR, have been known to be regulated by mechanisms related to inflammatory processes [25,28], and similar to existing literature, we show that they are upregulated in diabetic nephropathy [26,27,29].…”

Section: Discussionmentioning

confidence: 89%

“…However, changes in mRNA expression of PAFR in PBMCs were associated with the changes in mRNA expressions of other genes, namely CD36 [25,26], IP10 [27], and TIMP2 [28,29] in PBMCs. These genes, as well as PAFR, have been known to be regulated by mechanisms related to inflammatory processes [25,28], and similar to existing literature, we show that they are upregulated in diabetic nephropathy [26,27,29]. Considering that glomerular inflammation is an important factor in the progression of diabetic nephropathy [30,31], we can surmise that a common factor related thereto may be involved in the progression of nephropathy and upregulation of mRNA expression of PAFR in PBMCs.…”

Section: Discussionmentioning

confidence: 89%

Association between changes in the mRNA expression of platelet-activating factor receptor in peripheral blood mononuclear cells and progression of diabetic nephropathy

et al. 2019

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Introduction Several studies have recently pointed out the role of many inflammatory mediators in the progression of diabetes complications. We had previously demonstrated that mRNA expression of platelet-activating factor receptor (PAFR) in peripheral blood mononuclear cells (PBMCs) was associated with urinary albumin to creatinine ratio (ACR) and forearm flow-mediated dilatation in patients with type 2 diabetes. In an attempt to elucidate this association, patients were followed up for 1 year. Materials and methodsWe recruited 95 patients from the hospital outpatient clinic, among whom 86 were followed up for 1 year (normoalbuminuria: 40 patients, microalbuminuria: 25 patients, macroalbuminuria: 21 patients). We then measured their baseline and 12 month characteristics and collected blood samples to extract PBMCs and measure gene expressions. Results Despite higher mRNA expression of PAFR in PBMCs among patients with macroalbuminuria, the rise in its value was not associated with biomarkers of nephropathy, while baseline values were not associated with progression of nephropathy. Moreover, changes in mRNA expression of PAFR were correlated with changes in ACR in all patients (r = 0.225, p = 0.037) and estimated glomerular filtration rate in patients with macroalbuminuria (r = − 0.438, p = 0.047) during the follow-up period. Conclusion Our findings indicate that even though no causal relationship exists between diabetic nephropathy and elevated expression of PAFR in PBMCs, their close association signifies the presence of another common mechanism that could induce both events. Given these findings, the PAF/PAFR interaction could clarify corresponding mechanisms involved in diabetic complications.

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“…Our in vitro data, however, show an increased expression of Mmp16 and Adam1a and the decrease of Adamts2 during CGNs rescue [15]. To clarify the role of these enzymes, additional studies should be performed to investigate the neuroprotective effects of metalloproteinase inhibitors, like BB-94 [42] and marimastat [43], or activators like losartan [44].…”

Section: Enzymes Involved In Extracellular Matrix Remodelingmentioning

confidence: 81%

Drug target identification at the crossroad of neuronal apoptosis and survival

Maino

Paparone

Severini

et al. 2017

Expert Opinion on Drug Discovery

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Introduction: Inappropriate activation of apoptosis may contribute to neurodegeneration, a multifaceted process that results in various chronic disorders, including Alzheimer's and Parkinson's diseases. Several in vitro and in vivo studies demonstrated that neuronal apoptosis is a multi-pathway cell-death program that requires RNA synthesis. Thus, transcriptionally activated genes whose products induce cell death can be triggered by different stimuli and antagonized by neurotrophic factors. Systems biology is now unveiling the series of intracellular signaling pathways and key drug targets at the intersection of neuronal apoptosis and survival. Areas covered: This review introduces a genomic approach that can be used to elucidate the systems biology of neuronal apoptosis and survival, and to rationally select drug targets, no longer oriented to emulate the action of growth factors at the membrane receptor level, but rather to modulate their downstream signals. Expert opinion: The advent of genomics is offering an unprecedented opportunity to explore how the delicate balance between apoptosis and survival-inducing signals triggers a transcriptional program. Characterization of this program can be useful to identify potential pharmacological targets for existing drugs. Such knowledge might pave the way towards an innovative pharmacology. ARTICLE HISTORY

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Effect of Losartan on the mRNA Expressions of MT3-MMP and TIMP-2 in Diabetic Kidneys

Cited by 6 publications

References 14 publications

Physiological regulation of MMPs and tPA/PAI in the arterial wall of rats by noradrenergic tone and angiotensin II

Physiological regulation of MMPs and tPA/PAI in the arterial wall of rats by noradrenergic tone and angiotensin II

Association between changes in the mRNA expression of platelet-activating factor receptor in peripheral blood mononuclear cells and progression of diabetic nephropathy

Drug target identification at the crossroad of neuronal apoptosis and survival

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