Lovastatin Alleviates Endothelial-to-Mesenchymal Transition in Glomeruli via Suppression of Oxidative Stress and TGF-β1 Signaling

Ma, Zhuo; Zhu, Lili; Liu, Yan; Wang, Zhida; Yang, Yang; Chen, Liming; Lu, Qiulun

doi:10.3389/fphar.2017.00473

Cited by 29 publications

(31 citation statements)

References 40 publications

(48 reference statements)

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“…Accumulating evidence has shown that glomerular structural changes are diagnostic indicators for early DN. 25 In 2017, an investigation by Ma 26 These findings suggest that the levels of collagen and fibronectin are also increased in DN. Indeed, Masson's trichrome staining showed collagen accumulation in early-stage DN (Figure 1).…”

Section: Discussionmentioning

confidence: 99%

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Ramipril and resveratrol co‐treatment attenuates RhoA/ROCK pathway‐regulated early‐stage diabetic nephropathy‐associated glomerulosclerosis in streptozotocin‐induced diabetic rats

Xiang

Liang

et al. 2019

Environmental Toxicology

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Clinical studies have shown that hyperglycemia can induce early‐stage diabetic nephropathy (DN). Furthermore, oxidative stress, tubular epithelial‐mesenchymal transition and extracellular matrix accumulation promote the progression of DN to chronic kidney disease and tubulointerstitial fibrosis. It is necessary to initiate treatment at the early stages of DN or even during the early stages of diabetes. In this work, rats with streptozotocin (STZ)‐induced diabetes mellitus (DM) presented early DN symptoms within 45 days, and collagen accumulation in the glomerulus of the rats was primarily mediated through the RhoA/ROCK pathway instead of the TGF‐β signaling pathway. Resveratrol (15 mg/kg/day) and ramipril (10 mg/kg/day) co‐treatment of STZ‐induced DN rats showed that glomerulosclerosis in early‐stage DN was reversible (P < .05 compared with that in STZ‐induced DM rats). The results of this study support early intervention in diabetes or DN as a more efficient therapeutic strategy.

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Section: Discussionmentioning

confidence: 99%

“…Accumulating evidence has shown that glomerular structural changes are diagnostic indicators for early DN . In 2017, an investigation by Ma et al indicated that levels of TGF‐β1 and p‐Smad2/3 were increased in DN . These findings suggest that the levels of collagen and fibronectin are also increased in DN.…”

Section: Discussionmentioning

confidence: 99%

Ramipril and resveratrol co‐treatment attenuates RhoA/ROCK pathway‐regulated early‐stage diabetic nephropathy‐associated glomerulosclerosis in streptozotocin‐induced diabetic rats

Xiang

Liang

et al. 2019

Environmental Toxicology

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“…50 The clinically-approved cholesterol lowering agents, the "statins" family, diminish EMT, TGF-β signaling and oxidative stress in glomerular cells. 75,[154][155][156] Others (Figure 14). Therapeutic attempts have also included targeting histone H4 acetylation, NDI-010976/ND630 (123) RO6842262 (124) GLPG1690 (125) BMS-986020/AM152 (126) roflumilast (127) pentoxifylline (128) sildenafil (129) PF-00489791 (130) inhibition of the Ca 2+ -activated K + channel (KCa3.1), the mineralocorticoid/aldosterone receptors or the vitamin D-dependent pathways.…”

Section: Inhibitors Of Metabolic Pathways (mentioning

confidence: 99%

“…Erlotinib(74), the second approved EGFR inhibitor, reversibly binds to the ATP site of the receptor. Afatinib(75), is an irreversible covalent inhibitor of EGFR and ErbB-2/HER2. Lapatinib(76), is an orally active dual HER2/EGFR inhibitor of the ATPbinding pocket of the kinase domains.…”

mentioning

confidence: 99%

Fibrogenic Disorders in Human Diseases: From Inflammation to Organ Dysfunction

et al. 2018

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Fibrosis is an inadequate response to tissue stress with very few therapeutic options to prevent its progression to organ dysfunction. There is an urgent need to identify drugs with a therapeutic potential for fibrosis, either by designing and developing new compounds or by repurposing drugs already in clinical use which were developed for other indications. In this Perspective, we summarize some pathways and biological targets involved in fibrosis development and maintenance, focusing on common mechanisms between organs and diseases. We review the therapeutic agents under experimental development, clinical trials, or in clinical use for the treatment of fibrotic disorders, evaluating the reasons for the discrepancies observed between preclinical and clinical results. We also discuss the improvement that we envision in the development of therapeutic molecules able to achieve improved potential for treatment, including indirect modulators, targeting approaches, or drug combinations.

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“…The number of animal microvessels per group and eight fields of view per tissue were counted. All measurements were performed in a blinded manner [24].…”

Section: Pathologic Assessment Of Angiogenesismentioning

confidence: 99%

Pulsatility Index as a Novel Parameter for Perfusion in Mouse Model of Hindlimb Ischemia

Lü

Ding

et al. 2018

Cell Physiol Biochem

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Background/Aims: In clinical settings, the pulsatility index (PI) has become a widely used tool for monitoring obstetrics or other vascular diseases. It is based on the maximum Doppler shift waveform derived from ultrasonography. However, it remains unclear whether the PI levels are correctly predicted from the perfusion in mouse model of hindlimb ischemia. Methods: To explore the relationship between PI and perfusion, we generated a unilateral hindlimb ischemia model in 8-week-old C57BL/6 male mice by ligation of the right common iliac artery and femoral artery. These mice were monitored with laser Doppler perfusion imaging (LDPI) and an ultrasound system (Vevo2100). Vessel densities in ischemic skeletal muscles were measured with vWF staining, which functions as a marker for endothelial cells. In order to further verify PI evaluation in other conditions, we performed therapeutic experiments using hindlimb ischemic mouse with PBS or FGF2 treatment. Results: In the mouse model of hindlimb ischemia, the PI levels were continuously elevated and were accompanied by an increased ratio of perfusion to blood flow. 1 and 4 weeks after ischemia, the densities of vWF staining were correlated with PI values. Moreover, the PI index exactly reflected the perfusion in hindlimb ischemic mice after FGF2 treatment, while it indicated the condition of angiogenesis after therapeutic treatment based on the association between PI values and the number of vWF-positive stained cells in muscles. Conclusion: This study confirms the utility of a noninvasive and reproducible ultrasound index for a rapid evaluation of perfusion and blood recovery after hindlimb ischemia in vivo. PI, as one stable and comparable parameter, is correlated with angiogenesis in hindlimb ischemic mouse. Moreover, PI can exactly reflect perfusion and angiogenesis in therapeutic hindlimb ischemic mouse models. This study suggested that PI can serve as a novel index for relatively reproducible and repeatable blood flow recovery in the evaluation of emerging ischemic therapies and disease development in mouse models of hindlimb ischemia.

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Lovastatin Alleviates Endothelial-to-Mesenchymal Transition in Glomeruli via Suppression of Oxidative Stress and TGF-β1 Signaling

Cited by 29 publications

References 40 publications

Ramipril and resveratrol co‐treatment attenuates RhoA/ROCK pathway‐regulated early‐stage diabetic nephropathy‐associated glomerulosclerosis in streptozotocin‐induced diabetic rats

Ramipril and resveratrol co‐treatment attenuates RhoA/ROCK pathway‐regulated early‐stage diabetic nephropathy‐associated glomerulosclerosis in streptozotocin‐induced diabetic rats

Fibrogenic Disorders in Human Diseases: From Inflammation to Organ Dysfunction

Pulsatility Index as a Novel Parameter for Perfusion in Mouse Model of Hindlimb Ischemia

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