Replacement substance P reduces cardiac fibrosis in monkeys with type 2 diabetes

Meléndez, Giselle C.; Kavanagh, Kylie; Gharraee, Nazli; Lacy, Jessica L.; Goslen, Kevin; Block, Masha; Whitfield, Jordyn; Widiapradja, Alexander; Levick, Scott P.

doi:10.1016/j.biopha.2023.114365

Cited by 10 publications

(4 citation statements)

References 52 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In these experiments, mice were housed at a controlled temperature (25°C) and photoperiod (12 h:12 h light-dark cycle).Animal protocols were conducted in accordance with the NIH Guide for the Care and Use of Laboratory Animals (NIH Publication 85-23, revised 1996). Mice were divided into control (20) and DCM(100) group. During the 3months period of the study, DCM mice were fed a high fat and high sucrose diet, while control mice werefed a normal chow diet.Glucose tolerance tests (GTTs) and ELISA test which detected the blood glucose level and serum fasting insulin level were performed to confirm the mice had developed insulin resistance.…”

Section: Animal Protocolmentioning

confidence: 99%

“…Smad7 can block TGF-β1 signaling pathway through inhibiting the phosphorylation of Receptor Regulated Smads, such as Smad3 [19]. Large amounts of evidence have shown that down-regulating the expression of Smad7, myocardial fibrosis could significantly deteriorate [20].However, myocardial fibrosis induced by DCM cannot be effectively treated as of now.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Salvianolic Acid B (Sal B) ameliorates myocardial fibrosis in diabetic cardiomyopathy through deubiquitinating Smad7

Luo,

Fu,

Wang

et al. 2023

Preprint

View full text Add to dashboard Cite

Background Salvianolic acid B (Sal B), a water-soluble phenolic compound derived from Salvia Miltiorrhiza Bunge, is commonly used in Chinese Traditional Medicine for the treatment of cardiovascular diseases. Sal B has shown protecting effects against myocardial fibrosis induced by diabetic cardiomyopathy(DCM) in our previous experiment. This study aimed to investigate the ameliorative effects and potential mechanisms of Sal B in mitigating myocardial fibrosis induced by DCM. Methods In this study, a variety of methods were utilized to investigate the effects of Sal B on improving myocardial fibrosis induced by DCM in vivo and in vitro. These methods included weight measurement, blood glucose analysis, echocardiography, HE staining, Masson's trichrome staining, Sirius red staining, cell proliferation assessment, determination of hydroxyproline levels, immunohistochemical staining, evaluation of fibrosis-associated protein expression (Collagen I, Collagen III, TGF-β1, p-Smad3, Smad3, Smad7, and α-smooth muscle actin), analysis of Smad7 gene expression, and analysis of Smad7 ubiquitin modification. Results The animal test results indicated Sal B could significantly improve cardiac function, inhibit collagen deposition and phenotypic transformation, ameliorate myocardial fibrosis in DCM by up-regulating Smad7, thereby inhibiting TGF-β1 signaling pathway. Additionally, cell experiments demonstrated Sal B could significantly inhibit the proliferation, migration, phenotypic transformation and collagen secretion of cardiac fibroblasts (CFs) induced by high glucose(HG). Sal B could significantly decrease the ubiquitization modifications of Smad7, stabilize the protein expression of Smad7, therefore increase the protein expression of Smad7 in the CFs , inhibit TGF-β1 signaling pathway, that maybe a potential mechanism of Sal B in mitigating myocardial fibrosis induced by DCM. Conclusion In summary, this study revealed that Salvianolic acid B can improve myocardial fibrosis in DCM by deubiquitinating Smad7, stabilizing the protein expression of Smad7, blocking the TGF-β1 signaling pathway.

show abstract

Section: Animal Protocolmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Salvianolic Acid B (Sal B) ameliorates myocardial fibrosis in diabetic cardiomyopathy through deubiquitinating Smad7

Luo,

Fu,

Wang

et al. 2023

Preprint

View full text Add to dashboard Cite

show abstract

“…There are a multitude of observations detailing the role of substance P in fibrotic diseases in different tissues, including heart, lung, kidney, liver, and others. For example, after spinal cord surgery, substance P contributes to epidural fibrosis [4]. In the colon, substance P may play a role in chronic inflammation, evidenced in vivo through the neurokinin-1 receptor (NK-1R)-dependent activation of fibroblasts in accumulating at sites of inflammation, fibrosis, and inflammation, and in vitro by its ability to induce an increased expression of intracellular collagen and increased migration of a human-colon fibroblast cell line [5].…”

Section: Introductionmentioning

confidence: 99%

Potentiation of Collagen Deposition by the Combination of Substance P with Transforming Growth Factor Beta in Rat Skin Fibroblasts

Hilliard,

Amin,

Popoff

et al. 2024

IJMS

View full text Add to dashboard Cite

A role for substance P has been proposed in musculoskeletal fibrosis, with effects mediated through transforming growth factor beta (TGFβ). We examined the in vitro effects of substance P on proliferation, collagen secretion, and collagen deposition in rat primary dermal fibroblasts cultured in medium containing 10% fetal bovine serum, with or without TGFβ. In six-day cultures, substance P increased cell proliferation at concentrations from 0.0002 to 100 nM. TGFβ increased proliferation at concentrations from 0.0002 to 2 pg/mL, although higher concentrations inhibited proliferation. Substance P treatment alone at concentrations of 100, 0.2, and 0.00002 nM did not increase collagen deposition per cell, yet when combined with TGFβ (5 ng/mL), increased collagen deposition compared to TGFβ treatment alone. Substance P treatment (100 nM) also increased smooth muscle actin (SMA) expression at 72 h of culture at a level similar to 5 ng/mL of TGFβ; only TGFβ increased SMA at 48 h of culture. Thus, substance P may play a role in potentiating matrix deposition in vivo when combined with TGFβ, although this potentiation may be dependent on the concentration of each factor. Treatments targeting substance P may be a viable strategy for treating fibrosis where both substance P and TGFβ play roles.

show abstract

“…Smad7 can block the TGF-β1 signaling pathway by inhibiting the phosphorylation of receptor-regulated Smads, such as Smad3 [ 19 ]. Substantial evidence has shown that downregulating the expression of Smad7, myocardial fibrosis significantly deteriorate [ 20 ]. However, there are no effective treatment options for myocardial fibrosis induced by DCM currently.…”

Section: Introductionmentioning

confidence: 99%

Salvianolic acid B ameliorates myocardial fibrosis in diabetic cardiomyopathy by deubiquitinating Smad7

Luo,

Fu,

Wang

et al. 2023

Chin Med

View full text Add to dashboard Cite

Background Salvianolic acid B (Sal B), a water-soluble phenolic compound derived from Salvia miltiorrhiza Bunge, is commonly used in Traditional Chinese Medicine to treat cardiovascular disease. In our previous study, Sal B protected against myocardial fibrosis induced by diabetic cardiomyopathy (DCM). This study aimed to investigate the ameliorative effects and potential mechanisms of Sal B in mitigating myocardial fibrosis induced by DCM. Methods Various methods were used to investigate the effects of Sal B on myocardial fibrosis induced by DCM in vivo and in vitro. These methods included blood glucose measurement, echocardiography, HE staining, Masson’s trichrome staining, Sirius red staining, cell proliferation assessment, determination of hydroxyproline levels, immunohistochemical staining, evaluation of fibrosis-related protein expression (Collagen-I, Collagen-III, TGF-β1, p-Smad3, Smad3, Smad7, and α-smooth muscle actin), analysis of Smad7 gene expression, and analysis of Smad7 ubiquitin modification. Results The animal test results indicated that Sal B significantly improved cardiac function, inhibited collagen deposition and phenotypic transformation, and ameliorated myocardial fibrosis in DCM by upregulating Smad7, thereby inhibiting the TGF-β1 signaling pathway. In addition, cell experiments demonstrated that Sal B significantly inhibited the proliferation, migration, phenotypic transformation, and collagen secretion of cardiac fibroblasts (CFs) induced by high glucose (HG). Sal B significantly decreased the ubiquitination of Smad7 and stabilized the protein expression of Smad7, thereby increasing the protein expression of Smad7 in CFs and inhibiting the TGF-β1 signaling pathway, which may be the potential mechanism by which Sal B mitigates myocardial fibrosis induced by DCM. Conclusion This study revealed that Sal B can improve myocardial fibrosis in DCM by deubiquitinating Smad7, stabilizing the protein expression of Smad7, and blocking the TGF-β1 signaling pathway.

show abstract

Replacement substance P reduces cardiac fibrosis in monkeys with type 2 diabetes

Cited by 10 publications

References 52 publications

Salvianolic Acid B (Sal B) ameliorates myocardial fibrosis in diabetic cardiomyopathy through deubiquitinating Smad7

Salvianolic Acid B (Sal B) ameliorates myocardial fibrosis in diabetic cardiomyopathy through deubiquitinating Smad7

Potentiation of Collagen Deposition by the Combination of Substance P with Transforming Growth Factor Beta in Rat Skin Fibroblasts

Salvianolic acid B ameliorates myocardial fibrosis in diabetic cardiomyopathy by deubiquitinating Smad7

Contact Info

Product

Resources

About