scholarly journals Unanswered Questions Regarding Sex and BMP/TGF-β Signaling

2018 ◽  
Author(s):  
Tapan A. Shah ◽  
Melissa B. Rogers
Keyword(s):  
Signaling Pathways ◽  
Adult Life ◽  
Bmp Signaling ◽  
Current Understanding ◽  
Tgf Beta ◽  
Developmental Processes ◽  
Men And Women ◽  
Cardiovascular Pathologies

Crosstalk between the BMP and TGF-β signaling pathways regulates many complex developmental processes from the earliest stages of embryogenesis throughout adult life. In many situations, the two signaling pathways act reciprocally. For example, TGF-β signaling is generally pro-fibrotic whereas BMP signaling is anti-fibrotic and pro-calcific. Sex-specific differences occur in many diseases including cardiovascular pathologies. Differing ratios of fibrosis and calcification in stenotic valves suggests that BMP/TGF-β signaling may vary in men and women. In this review, we focus on the current understanding of the interplay between sex and BMP/TGF-β signaling and pose several unanswered questions.

scholarly journals The functions of ocu-miR-205 in regulating hair follicle development of Rex rabbits

2019 ◽  
Author(s):  
Gongyan Liu ◽  
Shu Li ◽  
Hongli Liu ◽  
Yanli Zhu ◽  
Liya Bai ◽  
...  
Keyword(s):  
Hair Follicle ◽  
Signaling Pathways ◽  
Adult Life ◽  
Hair Follicles ◽  
Bmp Signaling ◽  
Skin Tissue ◽  
Follicle Development ◽  
Hair Density ◽  
Phosphorylation Level ◽  
Hair Follicle Development

Abstract Background: Hair follicles is an appendage from the vertebrate skin epithelium, and arise from the embryonic ectoderm andregenerate cyclically during adult life. Dermal papilla cells (DPCs) is the key dermal component of the hair follicle that directly regulates hair follicle development, growth and regeneration. Recent studies have reported that miRNA plays an important role in regulating hair follicle morphogenesis, proliferation, differentiation and apoptosis of hair follicle stem cells. Results: The miRNAs expression profile of the DPCs from different hair density Rex rabbits shown that 240 differentially expressed of miRNAs were screened (log 2 (HD/LD)｜>1.00 and Q-value≤0.001). Among them, the expression of ocu-miR-205-5p in low hair densities DPCs was higher than that in high hair densities, and it is highly expressed in the skin tissue of Rex rabbits ( P <0.05). ocu-miR-205 could increase cell proliferation and cell apoptosis ratio, change cell cycle process ( P <0.05), affect the genes expression of PI3K/Akt, Wnt, Notch and BMP signaling pathways in DPCs and skin tissue of Rex rabbits, inhibit the protein phosphorylation level of CTNNB1, GSK-3β and the protein expression level of noggin (NOG), promote Akt phosphorylation level ( P <0.05). There was no significant change in primary follicle density ( P >0.05), but the secondary follicle density and total follicle density ( P <0.05) were changed after ocu-miR-205-5p interfered expression, and secondary/primary ratio (S/P) in ocu-miR-205-5p interfered expression group increased at 14 days after injection ( P <0.05). Conclusion: ocu-miR-205 could promote the apoptosis of DPCs, affect PI3K/Akt, Wnt, Notch and BMP signaling pathways genes and proteins expression in DPCs and skin of Rex rabbits, promote the transformation of hair follicles from growth phase to regression and resting phase, and affect hair density of Rex rabbits.

scholarly journals The functions of ocu-miR-205 in regulating hair follicle development in Rex rabbits

2020 ◽  
Author(s):  
Gongyan Liu ◽  
Shu Li ◽  
Hongli Liu ◽  
Yanli Zhu ◽  
Liya Bai ◽  
...  
Keyword(s):  
Hair Follicle ◽  
Signaling Pathways ◽  
Adult Life ◽  
Hair Follicles ◽  
Bmp Signaling ◽  
Skin Tissue ◽  
Follicle Development ◽  
Hair Density ◽  
Phosphorylation Level ◽  
Hair Follicle Development

Abstract Background: Hair follicles is an appendage from the vertebrate skin epithelium, and arise from the embryonic ectoderm andregenerate cyclically during adult life. Dermal papilla cells (DPCs) is the key dermal component of the hair follicle that directly regulates hair follicle development, growth and regeneration. Recent studies have reported that miRNA plays an important role in regulating hair follicle morphogenesis, proliferation, differentiation and apoptosis of hair follicle stem cells. Results: The miRNAs expression profile of the DPCs from different hair density Rex rabbits shown that 240 differentially expressed of miRNAs were screened (log 2 (HD/LD)｜>1.00 and Q-value≤0.001). Among them, the expression of ocu-miR-205-5p in low hair densities DPCs was higher than that in high hair densities, and it is highly expressed in the skin tissue of Rex rabbits ( P <0.05). ocu-miR-205 could increase cell proliferation and cell apoptosis ratio, change cell cycle process ( P <0.05), affect the genes expression of PI3K/Akt, Wnt, Notch and BMP signaling pathways in DPCs and skin tissue of Rex rabbits, inhibit the protein phosphorylation level of CTNNB1, GSK-3β and the protein expression level of noggin (NOG), promote Akt phosphorylation level ( P <0.05). There was no significant change in primary follicle density ( P >0.05), but the secondary follicle density and total follicle density ( P <0.05) were changed after ocu-miR-205-5p interfered expression, and secondary/primary ratio (S/P) in ocu-miR-205-5p interfered expression group increased at 14 days after injection ( P <0.05). Conclusion: ocu-miR-205 could promote the apoptosis of DPCs, affect PI3K/Akt, Wnt, Notch and BMP signaling pathways genes and proteins expression in DPCs and skin of Rex rabbits, promote the transformation of hair follicles from growth phase to regression and resting phase, and affect hair density of Rex rabbits.

scholarly journals The functions of ocu-miR-205 in regulating hair follicle development in Rex rabbits

2020 ◽  
Author(s):  
Gongyan Liu ◽  
Shu Li ◽  
Hongli Liu ◽  
Yanli Zhu ◽  
Liya Bai ◽  
...  
Keyword(s):  
Hair Follicle ◽  
Signaling Pathways ◽  
Adult Life ◽  
Hair Follicles ◽  
Bmp Signaling ◽  
Skin Tissue ◽  
Follicle Development ◽  
Hair Density ◽  
Phosphorylation Level ◽  
Hair Follicle Development

Abstract Background: Hair follicles is an appendage from the vertebrate skin epithelium, and arise from the embryonic ectoderm andregenerate cyclically during adult life. Dermal papilla cells (DPCs) is the key dermal component of the hair follicle that directly regulates hair follicle development, growth and regeneration. Recent studies have reported that miRNA plays an important role in regulating hair follicle morphogenesis, proliferation, differentiation and apoptosis of hair follicle stem cells. Results: The miRNAs expression profile of the DPCs from different hair density Rex rabbits shown that 240 differentially expressed of miRNAs were screened (log 2 (HD/LD)｜>1.00 and Q-value≤0.001). Among them, the expression of ocu-miR-205-5p in low hair densities DPCs was higher than that in high hair densities, and it is highly expressed in the skin tissue of Rex rabbits ( P <0.05). ocu-miR-205 could increase cell proliferation and cell apoptosis ratio, change cell cycle process ( P <0.05), affect the genes expression of PI3K/Akt, Wnt, Notch and BMP signaling pathways in DPCs and skin tissue of Rex rabbits, inhibit the protein phosphorylation level of CTNNB1, GSK-3β and the protein expression level of noggin (NOG), promote Akt phosphorylation level ( P <0.05). There was no significant change in primary follicle density ( P >0.05), but the secondary follicle density and total follicle density ( P <0.05) were changed after ocu-miR-205-5p interfered expression, and secondary/primary ratio (S/P) in ocu-miR-205-5p interfered expression group increased at 14 days after injection ( P <0.05). Conclusion: ocu-miR-205 could promote the apoptosis of DPCs, affect PI3K/Akt, Wnt, Notch and BMP signaling pathways genes and proteins expression in DPCs and skin of Rex rabbits, promote the transformation of hair follicles from growth phase to regression and resting phase, and affect hair density of Rex rabbits.

scholarly journals The functions of ocu-miR-205 in regulating hair follicle development in Rex rabbits

2020 ◽  
Author(s):  
Gongyan Liu ◽  
Shu Li ◽  
Hongli Liu ◽  
Yanli Zhu ◽  
Liya Bai ◽  
...  
Keyword(s):  
Hair Follicle ◽  
Signaling Pathways ◽  
Adult Life ◽  
Hair Follicles ◽  
Bmp Signaling ◽  
Skin Tissue ◽  
Follicle Development ◽  
Hair Density ◽  
Phosphorylation Level ◽  
Hair Follicle Development

Abstract Background: Hair follicles is an appendage from the vertebrate skin epithelium, and arise from the embryonic ectoderm andregenerate cyclically during adult life. Dermal papilla cells (DPCs) is the key dermal component of the hair follicle that directly regulates hair follicle development, growth and regeneration. Recent studies have reported that miRNA plays an important role in regulating hair follicle morphogenesis, proliferation, differentiation and apoptosis of hair follicle stem cells. Results: The miRNAs expression profile of the DPCs from different hair density Rex rabbits shown that 240 differentially expressed of miRNAs were screened (log 2 (HD/LD)｜>1.00 and Q-value≤0.001). Among them, the expression of ocu-miR-205-5p in low hair densities DPCs was higher than that in high hair densities, and it is highly expressed in the skin tissue of Rex rabbits ( P <0.05). ocu-miR-205 could increase cell proliferation and cell apoptosis ratio, change cell cycle process ( P <0.05), affect the genes expression of PI3K/Akt, Wnt, Notch and BMP signaling pathways in DPCs and skin tissue of Rex rabbits, inhibit the protein phosphorylation level of CTNNB1, GSK-3β and the protein expression level of noggin (NOG), promote Akt phosphorylation level ( P <0.05). There was no significant change in primary follicle density ( P >0.05), but the secondary follicle density and total follicle density ( P <0.05) were changed after ocu-miR-205-5p interfered expression, and secondary/primary ratio (S/P) in ocu-miR-205-5p interfered expression group increased at 14 days after injection ( P <0.05). Conclusion: ocu-miR-205 could promote the apoptosis of DPCs, affect PI3K/Akt, Wnt, Notch and BMP signaling pathways genes and proteins expression in DPCs and skin of Rex rabbits, promote the transformation of hair follicles from growth phase to regression and resting phase, and affect hair density of Rex rabbits.

scholarly journals The functions of ocu-miR-205 in regulating hair follicle development in Rex rabbits

2020 ◽  
Author(s):  
Gongyan Liu ◽  
Shu Li ◽  
Hongli Liu ◽  
Yanli Zhu ◽  
Liya Bai ◽  
...  
Keyword(s):  
Hair Follicle ◽  
Signaling Pathways ◽  
Adult Life ◽  
Hair Follicles ◽  
Bmp Signaling ◽  
Skin Tissue ◽  
Follicle Development ◽  
Hair Density ◽  
Phosphorylation Level ◽  
Hair Follicle Development

Abstract Background: Hair follicles is an appendage from the vertebrate skin epithelium, and arise from the embryonic ectoderm andregenerate cyclically during adult life. Dermal papilla cells (DPCs) is the key dermal component of the hair follicle that directly regulates hair follicle development, growth and regeneration. Recent studies have reported that miRNA plays an important role in regulating hair follicle morphogenesis, proliferation, differentiation and apoptosis of hair follicle stem cells. Results: The miRNAs expression profile of the DPCs from different hair density Rex rabbits shown that 240 differentially expressed of miRNAs were screened (log 2 (HD/LD)｜>1.00 and Q-value≤0.001). Among them, the expression of ocu-miR-205-5p in low hair densities DPCs was higher than that in high hair densities, and it is highly expressed in the skin tissue of Rex rabbits ( P <0.05). ocu-miR-205 could increase cell proliferation and cell apoptosis ratio, change cell cycle process ( P <0.05), affect the genes expression of PI3K/Akt, Wnt, Notch and BMP signaling pathways in DPCs and skin tissue of Rex rabbits, inhibit the protein phosphorylation level of CTNNB1, GSK-3β and the protein expression level of noggin (NOG), promote Akt phosphorylation level ( P <0.05). There was no significant change in primary follicle density ( P >0.05), but the secondary follicle density and total follicle density ( P <0.05) were changed after ocu-miR-205-5p interfered expression, and secondary/primary ratio (S/P) in ocu-miR-205-5p interfered expression group increased at 14 days after injection ( P <0.05). Conclusion: ocu-miR-205 could promote the apoptosis of DPCs, affect PI3K/Akt, Wnt, Notch and BMP signaling pathways genes and proteins expression in DPCs and skin of Rex rabbits, promote the transformation of hair follicles from growth phase to regression and resting phase, and affect hair density of Rex rabbits.

scholarly journals The functions of ocu-miR-205 in regulating hair follicle development in Rex rabbits

2020 ◽  
Author(s):  
Gongyan Liu ◽  
Shu Li ◽  
Hongli Liu ◽  
Yanli Zhu ◽  
Liya Bai ◽  
...  
Keyword(s):  
Hair Follicle ◽  
Signaling Pathways ◽  
Adult Life ◽  
Hair Follicles ◽  
Bmp Signaling ◽  
Skin Tissue ◽  
Follicle Development ◽  
Hair Density ◽  
Phosphorylation Level ◽  
Hair Follicle Development

Abstract Background: Hair follicles is an appendage from the vertebrate skin epithelium, and arise from the embryonic ectoderm andregenerate cyclically during adult life. Dermal papilla cells (DPCs) is the key dermal component of the hair follicle that directly regulates hair follicle development, growth and regeneration. Recent studies have reported that miRNA plays an important role in regulating hair follicle morphogenesis, proliferation, differentiation and apoptosis of hair follicle stem cells. Results: The miRNAs expression profile of the DPCs from different hair density Rex rabbits shown that 240 differentially expressed of miRNAs were screened (log 2 (HD/LD)｜>1.00 and Q-value≤0.001). Among them, the expression of ocu-miR-205-5p in low hair densities DPCs was higher than that in high hair densities, and it is highly expressed in the skin tissue of Rex rabbits ( P <0.05). ocu-miR-205 could increase cell proliferation and cell apoptosis ratio, change cell cycle process ( P <0.05), affect the genes expression of PI3K/Akt, Wnt, Notch and BMP signaling pathways in DPCs and skin tissue of Rex rabbits, inhibit the protein phosphorylation level of CTNNB1, GSK-3β and the protein expression level of noggin (NOG), promote Akt phosphorylation level ( P <0.05). There was no significant change in primary follicle density ( P >0.05), but the secondary follicle density and total follicle density ( P <0.05) were changed after ocu-miR-205-5p interfered expression, and secondary/primary ratio (S/P) in ocu-miR-205-5p interfered expression group increased at 14 days after injection ( P <0.05). Conclusion: ocu-miR-205 could promote the apoptosis of DPCs, affect PI3K/Akt, Wnt, Notch and BMP signaling pathways genes and proteins expression in DPCs and skin of Rex rabbits, promote the transformation of hair follicles from growth phase to regression and resting phase, and affect hair density of Rex rabbits.

scholarly journals Mechanism of CK2.3, a Novel Mimetic Peptide of Bone Morphogenetic Protein Receptor Type IA, Mediated Osteogenesis

2019 ◽  
Vol 20 (10) ◽  
pp. 2500 ◽  
Author(s):  
Vrathasha Vrathasha ◽  
Hilary Weidner ◽  
Anja Nohe
Keyword(s):  
Signaling Pathways ◽  
Treatment Options ◽  
Time Frame ◽  
Bmp Signaling ◽  
C2c12 Cells ◽  
Molecular Sequence ◽  
Sequence Of Events ◽  
Protein Receptor

Background: Osteoporosis is a degenerative skeletal disease with a limited number of treatment options. CK2.3, a novel peptide, may be a potential therapeutic. It induces osteogenesis and bone formation in vitro and in vivo by acting downstream of BMPRIA through releasing CK2 from the receptor. However, the detailed signaling pathways, the time frame of signaling, and genes activated remain largely unknown. Methods: Using a newly developed fluorescent CK2.3 analog, specific inhibitors for the BMP signaling pathways, Western blot, and RT-qPCR, we determined the mechanism of CK2.3 in C2C12 cells. We then confirmed the results in primary BMSCs. Results: Using these methods, we showed that CK2.3 stimulation activated OSX, ALP, and OCN. CK2.3 stimulation induced time dependent release of CK2β from BMPRIA and concurrently CK2.3 colocalized with CK2α. Furthermore, CK2.3 induced BMP signaling depends on ERK1/2 and Smad1/5/8 signaling pathways. Conclusion: CK2.3 is a novel peptide that drives osteogenesis, and we detailed the molecular sequence of events that are triggered from the stimulation of CK2.3 until the induction of mineralization. This knowledge can be applied in the development of future therapeutics for osteoporosis.

Abstract 312: Regulation of Fibrotic Signaling Pathways by Desmosomal Armadillo Proteins in Cardiac Tissue

2014 ◽  
Vol 115 (suppl_1) ◽  
Author(s):  
Adi D Dubash ◽  
Kathleen J Green
Keyword(s):  
Gene Expression ◽  
Signaling Pathways ◽  
Cardiac Disease ◽  
Cardiac Tissue ◽  
Cardiac Fibroblasts ◽  
Fibrous Tissue ◽  
Tgf Beta ◽  
Extracellular Matrix Components ◽  
Different Types ◽  
P38mapk Signaling

The process of fibrosis, described as accumulation of myofibroblasts and excessive deposition of extracellular matrix components, is a key development in the progression of multiple different types of cardiac disease. Nevertheless, little is known about the molecular mechanisms which cause the onset of fibrosis in cardiac disease. Fibrosis is a significant component of arrhythmogenic cardiomyopathy (AC), a genetic disorder characterized by replacement of healthy cardiomyocytes (CMs) with fibrous tissue, leading to arrhythmia and in certain cases, sudden death. AC is often characterized as a “disease of the desmosome”, as mutations for all obligate desmosome proteins have been found in cases of AC, including the desmosome armadillo proteins Plakophilin-2 (PKP2) and Plakoglobin (PG). PKP2 and PG are multi-functional proteins involved in both mechanical stabilization of the cardiac area composita, as well as mediation of desmosome-related signaling pathways. We have determined that loss of PKP2 or PG in neonatal CMs causes an aberrant increase in gene expression of pro-fibrotic stimuli such as transforming growth factor beta 1 (TGF-beta1) and Interleukin-6 (IL-6). In addition, p38 MAPK, a known mediator of inflammatory fibrosis, is activated upon loss of PKP2/PG. We hypothesize that mutation or loss of PKP2 or PG cause the recruitment and activation of cardiac fibroblasts via pro-fibrotic TGF-beta and p38MAPK signaling, resulting in pathological fibrosis characteristic of AC. Indeed, conditioned media from PKP2-silenced CMs causes an increase in fibronectin gene expression by freshly isolated cardiac fibroblasts. Our future experiments will investigate whether inhibition of TGF-beta or p38MAPK signaling can alleviate fibrotic gene production. By highlighting a novel link between desmosome armadillo proteins and pro-fibrotic signaling in cardiac tissue, this study provides mechanistic insights into the pathogenesis of AC, as well as advances our knowledge of potential therapeutic targets for combating fibrosis in multiple different types of heart disease or injury.

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