The protective effects of bone morphogenetic protein-7 against epithelial injury and matrix metalloproteases upregulation induced by silica in vitro

Liang, Dan; An, Gary; Zhu, Zhaohui; Wang, Y; Yang, Gui-Zhen; Li, X; Niu, Piye; Chen, L; Tian, Lei

doi:10.1177/0960327116674527

Cited by 4 publications

(2 citation statements)

References 40 publications

(54 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Our results of BMP-7 reduced adverse myocardial remodeling MMP9 marker, hypertrophy as well as interstitial and vascular fibrosis. There is only one study that showed BMP-7 reduced MMP9 in an inflammatory silica-induced lung cell line in vitro [54]. Therefore, it is possible that BMP-7 reduced cardiac fibrosis and adverse myocardial remodeling through transforming growth factor (TGF-β1) [4,[35][36][37].…”

Section: Discussionmentioning

confidence: 99%

BMP-7 Attenuates Inflammation-Induced Pyroptosis and Improves Cardiac Repair in Diabetic Cardiomyopathy

Elmadbouh

Singla

2021

Cells

View full text Add to dashboard Cite

In the present study, we investigated a novel signaling target in diabetic cardiomyopathy where inflammation induces caspase-1-dependent cell death, pyroptosis, involving Nek7-GBP5 activators to activate the NLRP3 inflammasome, destabilizes cardiac structure and neovascularization. Furthermore, we explored the therapeutic ability of bone morphogenetic protein-7 (BMP-7) to attenuate these adverse effects. C57BL/6J mice (n = 16 mice/group) were divided into: control (200 mg/kg, 0.9% saline intraperitoneal injection, i.p.); Streptozotocin (STZ) and STZ-BMP-7 groups (STZ, 200 mg/kg, i.p. injection). After 6 weeks, heart function was examined with echocardiography, and mice were sacrificed. Immunostaining, Western blotting, H&E, and Masson’s trichrome staining was performed on heart tissues. STZ-induced diabetic cardiomyopathy significantly increased inflammasome formation (TLR4, NLRP3, Nek7, and GBP5), pyroptosis markers (caspase-1, IL-1β, and IL-18), inflammatory cytokines (IL-6 and TNF-α), MMP9, and infiltration of monocytes (CD14), macrophage (iNOS), and dendritic cells (CD11b and CD11c) (p < 0.05). Moreover, a significant endothelial progenitor cells (EPCs) dysfunction (c-Kit/FLk-1, CD31), adverse cardiac remodeling, and reduction in left ventricular (LV) heart function were observed in STZ versus control (p < 0.05). Treatment with BMP-7 significantly reduced inflammasome formation, pyroptosis, and inflammatory cytokines and infiltrated inflammatory cells. In addition, BMP-7 treatment enhanced EPC markers and neovascularization and subsequently improved cardiac remodeling in a diabetic heart. Moreover, a significant improvement in LV heart function was achieved after BMP-7 administration relative to diabetic mice (p < 0.05). In conclusion, BMP-7 attenuated inflammation-induced pyroptosis, adverse cardiac remodeling, and improved heart function via the TLR4-NLRP3 inflammasome complex activated by novel signaling Nek7/GBP5. Our BMP-7 pre-clinical studies of mice could have significant potential as a future therapy for diabetic patients.

show abstract

Section: Discussionmentioning

confidence: 99%

BMP-7 Attenuates Inflammation-Induced Pyroptosis and Improves Cardiac Repair in Diabetic Cardiomyopathy

Elmadbouh

Singla

2021

Cells

View full text Add to dashboard Cite

show abstract

“…Therefore, inhibiting TGF-β1-mediated signaling may be a promising therapeutic option for treating patients with RIF. Previously, BMP-7 has been demonstrated to antagonize TGF-β1-mediated fibrosis through the suppression of EMT in fibroses of a number of different organs, including the lung and liver (29)(30)(31)(32). However, the effects of BMP-7 on EMT in RIF have not yet been determined previously.…”

Section: Discussionmentioning

confidence: 99%

Overexpression of BMP‑7 reverses TGF‑β1‑induced epithelial‑mesenchymal transition by attenuating the Wnt3/β‑catenin and/Smad2/3 signaling pathways in HK‑2 cells

Song

Wang

et al. 2019

Mol Med Report

View full text Add to dashboard Cite

Tubular epithelial cells undergoing epithelial-mesenchymal transition (eMT) is a crucial event in the progression of renal interstitial fibrosis (RIF). Bone morphogenetic protein-7 (BMP-7) has been reported to exhibit anti-fibrotic functions in various renal diseases. However, the function of BMP-7 in regulating EMT and the progression of RIF remains largely unknown. The aim of the present study was to examine the potential effect of BMP-7 on transforming growth factor β1 (TGF-β1)-induced eMT and the underlying mechanisms by which BMP-7 exerted its effects. Human renal proximal tubular epithelial cells (HK-2) were treated with TGF-β1 for various time periods and at various concentrations and lentiviral vectors were used to overexpress BMP-7. Cell Counting Kit-8 and Transwell assays were used to evaluate the viability and migration of HK-2 cells in vitro. EMT was estimated by assessing the changes in cell morphology and the expression of EMT markers. In addition, the activation of the Wnt3/β-catenin and TGF-β1/Smad2/3 signaling pathways were analyzed using western blotting. TGF-β1 induced eMT in a time-and dose-dependent manner in HK-2 cells. Treatment with TGF-β1 induced morphological changes, decreased cell viability and the expression of E-cadherin, increased cell migration and the expression of α-smooth muscle actin, fibroblast-specific protein 1, collagen I and vimentin, and activated the Wnt3/β-catenin and TGF-β1/Smad2/3 signaling pathways in HK-2 cells. However, BMP-7 overexpression notably reversed all these effects. These results suggest that BMP-7 effectively suppresses TGF-β1-induced eMT through the inhibition of the Wnt3/β-catenin and TGF-β1/Smad2/3 signaling pathways, highlighting a potential novel anti-RIF strategy.

show abstract

Emerging role of BMPs/BMPR2 signaling pathway in treatment for pulmonary fibrosis

Ye,

Taleb,

Zhao

et al. 2024

Biomedicine & Pharmacotherapy

View full text Add to dashboard Cite

The protective effects of bone morphogenetic protein-7 against epithelial injury and matrix metalloproteases upregulation induced by silica in vitro

Cited by 4 publications

References 40 publications

BMP-7 Attenuates Inflammation-Induced Pyroptosis and Improves Cardiac Repair in Diabetic Cardiomyopathy

BMP-7 Attenuates Inflammation-Induced Pyroptosis and Improves Cardiac Repair in Diabetic Cardiomyopathy

Overexpression of BMP‑7 reverses TGF‑β1‑induced epithelial‑mesenchymal transition by attenuating the Wnt3/β‑catenin and/Smad2/3 signaling pathways in HK‑2 cells

Emerging role of BMPs/BMPR2 signaling pathway in treatment for pulmonary fibrosis

Contact Info

Product

Resources

About