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1.
Plant Cell Rep ; 43(8): 204, 2024 Jul 30.
Article in English | MEDLINE | ID: mdl-39080060

ABSTRACT

In plants, nitric oxide (NO) has been widely accepted as a signaling molecule that plays a role in different processes. Among the most relevant pathways by which NO and its derivatives realize their biological functions, post-translational protein modifications are worth mentioning. Protein S-nitrosylation has been the most studied NO-dependent regulatory mechanism; it is emerging as an essential mechanism for transducing NO bioactivity in plants and animals. In recent years, the research of protein S-nitrosylation in plant growth and development has made significant progress, including processes such as seed germination, root development, photosynthetic regulation, flowering regulation, apoptosis, and plant senescence. In this review, we focus on the current state of knowledge on the role of S-nitrosylation in plant growth and development and provide a better understanding of its action mechanisms.


Subject(s)
Nitric Oxide , Plant Development , Plant Proteins , Protein Processing, Post-Translational , Nitric Oxide/metabolism , Plant Proteins/metabolism , Plant Proteins/genetics , Plants/metabolism , Germination , Photosynthesis , Plant Roots/metabolism , Plant Roots/growth & development , Signal Transduction
2.
Int J Biol Macromol ; 273(Pt 1): 133084, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38871104

ABSTRACT

Salinity hinders plant growth and development, resulting in reduced crop yields and diminished crop quality. Nitric oxide (NO) and brassinolides (BR) are plant growth regulators that coordinate a plethora of plant physiological responses. Nonetheless, the way in which these factors interact to affect salt tolerance is not well understood. BR is perceived by the BR receptor BRASSINOSTEROID INSENSITIVE 1 (BRI1) and its co-receptor BRI1-associated kinase 1 (BAK1) to form the receptor complex, eventually inducing BR-regulated responses. To response stress, a wide range of NO-mediated protein modifications is undergone in eukaryotic cells. Here, we showed that BR participated in NO-enhanced salt tolerance of tomato seedlings (Solanum lycopersicum cv. Micro-Tom) and NO may activate BR signaling under salt stress, which was related to NO-mediated S-nitrosylation. Further, in vitro and in vivo results suggested that BAK1 (SERK3A and SERK3B) was S-nitrosylated, which was inhibited under salt condition and enhanced by NO. Accordingly, knockdown of SERK3A and SERK3B reduced the S-nitrosylation of BAK1 and resulted in a compromised BR response, thereby abolishing NO-induced salt tolerance. Besides, we provided evidence for the interaction between BRI1 and SERK3A/SERK3B. Meanwhile, NO enhanced BRI1-SERK3A/SERK3B interaction. These results imply that NO-mediated S-nitrosylation of BAK1 enhances the interaction BRI1-BAK1, facilitating BR response and subsequently improving salt tolerance in tomato. Our findings illustrate a mechanism by which redox signaling and BR signaling coordinate plant growth in response to abiotic stress.


Subject(s)
Nitric Oxide , Plant Proteins , Salt Tolerance , Seedlings , Solanum lycopersicum , Solanum lycopersicum/metabolism , Solanum lycopersicum/genetics , Seedlings/metabolism , Salt Tolerance/genetics , Nitric Oxide/metabolism , Plant Proteins/metabolism , Plant Proteins/genetics , Brassinosteroids/metabolism , Protein Serine-Threonine Kinases/metabolism , Protein Serine-Threonine Kinases/genetics , Gene Expression Regulation, Plant , Salt Stress , Signal Transduction
3.
Int J Mol Sci ; 25(3)2024 Feb 05.
Article in English | MEDLINE | ID: mdl-38339212

ABSTRACT

Growing evidence suggests that exposure of plants to unfavorable environments leads to the accumulation of hydrogen sulfide (H2S) and reactive oxygen species (ROS). H2S interacts with the ROS-mediated oxidative stress response network at multiple levels. Therefore, it is essential to elucidate the mechanisms by which H2S and ROS interact. The molecular mechanism of action by H2S relies on the post-translational modification of the cysteine sulfur group (-SH), known as persulfidation. H2S cannot react directly with -SH, but it can react with oxidized cysteine residues, and this oxidation process is induced by H2O2. Evidently, ROS is involved in the signaling pathway of H2S and plays a significant role. In this review, we summarize the role of H2S-mediated post-translational modification mechanisms in oxidative stress responses. Moreover, the mechanism of interaction between H2S and ROS in the regulation of redox reactions is focused upon, and the positive cooperative role of H2S and ROS is elucidated. Subsequently, based on the existing evidence and clues, we propose some potential problems and new clues to be explored, which are crucial for the development of the crosstalk mechanism of H2S and ROS in plants.


Subject(s)
Hydrogen Sulfide , Hydrogen Sulfide/metabolism , Reactive Oxygen Species/metabolism , Cysteine/metabolism , Hydrogen Peroxide/metabolism , Oxidative Stress , Oxidation-Reduction , Plants/metabolism
4.
Can J Infect Dis Med Microbiol ; 2024: 7547514, 2024.
Article in English | MEDLINE | ID: mdl-38283082

ABSTRACT

Background: The potential role of cell envelope integrity proteins in mediating antibiotic resistance is not well understood. In this study, we investigated whether the cell envelope integrity protein D0Y85_RS06240 from the multiantibiotic resistant strain Stenotrophomonas sp. G4 mediates antibiotic resistance. Methods: Bioinformatics analysis was conducted to identify proteins related to the D0Y85_RS06240 protein. The D0Y85_RS06240 gene was heterologously expressed in Escherichia coli, both antibiotic MICs and the effect of efflux pump inhibitors on antibiotic MICs were determined by the broth microdilution method. A combination of antibiotic and efflux pump inhibitor was used to investigate bacterial killing kinetics, and binding of D0Y85_RS06240 to antibiotic molecules was predicted by molecular docking analysis. Results: Sequence homology analysis revealed that D0Y85_RS06240 was related to cell envelope integrity proteins. The D0Y85_RS06240 heterologous expression strains were resistant to multiple antibiotics, including colistin, tetracycline, and cefixime. However, the efflux pump inhibitor N-methylpyrrolidone (NMP) reduced the antibiotic MICs of the D0Y85_RS06240 heterologous expression strain, and bacterial killing kinetics revealed that NMP enhanced the bactericidal rate of tetracycline to the drug-resistant bacteria. Molecular docking analysis indicated that D0Y85_RS06240 could bind colistin, tetracycline, and cefixime. Conclusion: The cell envelope integrity protein D0Y85_RS06240 in Stenotrophomonas sp. G4 mediates multiantibiotic resistance. This study lays the foundation for an in-depth analysis of D0Y85_RS06240-mediated antibiotic resistance mechanisms and the use of D0Y85_RS06240 as a target for the treatment of multiantibiotic-resistant bacterial infections.

5.
Mol Oncol ; 17(10): 2056-2073, 2023 10.
Article in English | MEDLINE | ID: mdl-37558205

ABSTRACT

During epithelial-mesenchymal transition (EMT) in cancer progression, tumor cells switch cadherin profile from E-cadherin to cadherin-11 (CDH11), which is accompanied by increased invasiveness and metastatic activity. However, the mechanism through which CDH11 may affect tumor growth and metastasis remains elusive. Here, we report that CDH11 was highly expressed in multiple human tumors and was localized on the membrane, in the cytoplasm and, surprisingly, also in the nucleus. Interestingly, ß-catenin remained bound to carboxy-terminal fragments (CTFs) of CDH11, the products of CDH11 cleavage, and co-localized with CTFs in the nucleus in the majority of breast cancer samples. Binding of ß-catenin to CTFs preserved ß-catenin activity, whereas inhibiting CDH11 cleavage led to ß-catenin phosphorylation and diminished Wnt signaling, similar to CDH11 knockout. Our data elucidate a previously unknown role of CDH11, which serves to stabilize ß-catenin in the cytoplasm and facilitates its translocation to the nucleus, resulting in activation of Wnt signaling, with subsequent increased proliferation, migration and invasion potential.


Subject(s)
Neoplasms , beta Catenin , Humans , beta Catenin/metabolism , Wnt Signaling Pathway , Cadherins/metabolism , Cell Proliferation , Epithelial-Mesenchymal Transition , Cell Line, Tumor , Cell Movement
6.
Nitric Oxide ; 138-139: 51-63, 2023 09 01.
Article in English | MEDLINE | ID: mdl-37364740

ABSTRACT

Carbon monoxide (CO) has been recognized as a crucial gasotransmitter mainly produced by heme oxygenase (HO)-catalyzed heme degradation in plant. Recent studies have shown that CO plays an important role in regulating growth and development of plant, as well as and responding to a variety of abiotic stresses. Meanwhile, many studies have reported on CO working in combination with other signal molecules to mitigate abiotic stress. Here, we presented a comprehensive overview of recent developments in which CO reduces plant damage caused by abiotic stresses. The regulation of antioxidant system, photosynthetic system, ion balance and transport are the main mechanisms of CO-alleviated abiotic stress. We also proposed and discussed the relationship between CO and other signal molecules, including nitric oxide (NO), hydrogen sulfide (H2S), hydrogen gas (H2), abscisic acid (ABA), indole 3-acetic acid (IAA), gibberellin (GA), cytokine (CTK), salicylic acid (SA), jasmonic acid (JA), hydrogen peroxide (H2O2) and calcium ion (Ca2+). Furthermore, the important role of HO genes in alleviating abiotic stress was also discussed. We proposed promising and new research directions for the study of plant CO, which can provide further insights on the role of CO in plant growth and development under abiotic stress.


Subject(s)
Heme , Hydrogen Sulfide , Carbon Monoxide/metabolism , Hydrogen Peroxide/metabolism , Hydrogen Sulfide/metabolism , Stress, Physiological , Plants/metabolism , Heme Oxygenase (Decyclizing)
7.
Front Microbiol ; 14: 1188900, 2023.
Article in English | MEDLINE | ID: mdl-37283918

ABSTRACT

Introduction: The role of integrative and conjugative elements (ICEs) in antibiotic resistance in Morganella morganii is unknown. This study aimed to determine whether an ICE identified in the M. morganii genome contributed to the polymyxin resistance. Methods: Whole-genome sequencing was performed followed by bioinformatics analyses to identify ICEs and antibiotic resistance genes. Conjugation assays were performed to analyze the transferability of a discovered ICE. A drug transporter encoded on the ICE was heterogeneously expressed in Escherichia coli, minimum inhibitory concentrations of antibiotics were determined, and a traditional Chinese medicine library was screened for potential efflux pump inhibitors. Results: An antibiotic resistance-conferring ICE, named ICEMmoMP63, was identified. ICEMmoMP63 was verified to be horizontally transferred among Enterobacteriaceae bacteria. G3577_03020 in ICEMmoMP63 was found to mediate multiple antibiotic resistances, especially polymyxin resistance. However, natural compound glabridin was demonstrated to inhibit polymyxin resistance. Discussion: Our findings support the need for monitoring dissemination of ICEMmoMP63 in Enterobacteriaceae bacteria. Combined glabridin and polymyxin may have therapeutic potential for treating infections from multi-drug resistant bacteria carrying ICEMmoMP63.

8.
Microorganisms ; 11(4)2023 Apr 14.
Article in English | MEDLINE | ID: mdl-37110447

ABSTRACT

Composting, planting, and breeding waste for return to the field is the most crucial soil improvement method under the resource utilization of agricultural waste. However, how the vegetable yield and rhizosphere soil environment respond to different composts is still unknown. Therefore, eight formulations were designed for compost fermentation using agricultural waste [sheep manure (SM), tail vegetable (TV), cow manure (CM), mushroom residue (MR), and corn straw (CS)] without fertilizer (CK1) and local commercial organic fertilizer (CK2) as controls to study the yield and rhizosphere soil environment of greenhouse zucchini in response to different planting and breeding waste compost. Applying planting and breeding waste compost significantly increased the soil's organic matter and nutrient content. It inhibited soil acidification, which T4 (SM:TV:CS = 6:3:1) and T7 (SM:TV:MR:CS = 6:2:1:1) treatments affected significantly. Compared to CK2 treatment, T4 and T7 treatments showed a greater increase, with a significant increase of 14.69% and 11.01%, respectively. Therefore, T4, T7, and two control treatments were selected for high-throughput sequencing based on yield performance. Compared with the CK1 treatment, although multiple applications of chemical fertilizers led to a decrease in bacterial and fungal richness, planting and breeding waste compost maintained bacterial diversity and enhanced fungal diversity. Compared to CK2, the relative abundance increased in T7-treated Proteobacteria (Sphingomonas, Pseudomonas, and Lysobacter) and T4-treated Bacteroidetes (Flavobacterium) among bacteria. An increase in T4-treated Ascomycota (Zopfiella and Fusarium) and Basidiomycota among fungi and a decrease in T7-treated Mortierellomycota have been observed. Functional predictions of the bacterial Tax4Fun and fungal FUNGuild revealed that applying planting and breeding waste compost from the T4 treatment significantly increased the abundance of soil bacterial Metabolism of Cities, Genetic Information Processing, and Cellular Processes decreased the abundance of Pathotroph and Saprotroph-Symbiotroph fungi and increased the abundance of Saprotroph fungi. Overall, planting and breeding waste compost increased zucchini yield by improving soil fertility and microbial community structure. Among them, T4 treatment has the most significant effect, so T4 treatment can be selected as the optimized formulation of local commercial organic fertilizer. These findings have valuable implications for sustainable agricultural development.

9.
Int J Mol Sci ; 23(14)2022 Jul 11.
Article in English | MEDLINE | ID: mdl-35887014

ABSTRACT

Salt stress impairs plant growth and development, thereby causing low yield and inferior quality of crops. In this study, tomato (Solanum lycopersicum L. 'Micro-Tom') seedlings treated with different concentrations of sodium chloride (NaCl) were investigated in terms of decreased plant height, stem diameter, dry weight, fresh weight, leaves relative water content and root activity. To reveal the response mechanism of tomato seedlings to salt stress, the transcriptome of tomato leaves was conducted. A total of 6589 differentially expressed genes (DEGs) were identified and classified into different metabolic pathways, especially photosynthesis, carbon metabolism, biosynthesis of amino acids and mitogen-activated protein kinase (MAPK) signaling pathway. Of these, approximately 42 DEGs were enriched in the MAPK signaling pathway, most of which mainly included plant hormone, hydrogen peroxide (H2O2), wounding and pathogen infection signaling pathways. To further explore the roles of MAPK under salt stress, MAPK phosphorylation inhibitor SB203580 (SB) was applied. We found that SB further decreased endogenous jasmonic acid, abscisic acid and ethylene levels under salt stress condition. Additionally, in comparison with NaCl treatment alone, SB + NaCl treatment reduced the content of O2- and H2O2 and the activities of antioxidant enzyme and downregulated the expression levels of genes related to pathogen infection. Together, the results revealed that MAPK might be involved in the salinity response of tomato seedlings by regulating hormone balance, ROS metabolism, antioxidant capacity and plant immunity.


Subject(s)
Seedlings , Solanum lycopersicum , Antioxidants/metabolism , Hydrogen Peroxide/metabolism , Solanum lycopersicum/metabolism , Mitogen-Activated Protein Kinases/genetics , Mitogen-Activated Protein Kinases/metabolism , Salt Stress , Seedlings/metabolism , Sodium Chloride/metabolism , Sodium Chloride/pharmacology , Stress, Physiological
10.
Front Plant Sci ; 13: 822956, 2022.
Article in English | MEDLINE | ID: mdl-35783924

ABSTRACT

Volatile compounds could affect the flavor and ornamental quality of cut flowers, but the flavor change occurring during the vase period of the cut flower is unclear. To clarify the dynamic changes during the vase period of cut lily (Lilium spp. 'Manissa') flowers, comprehensive flavor profiles were characterized by the electronic nose (E-nose) and headspace solid-phase microextraction gas chromatography-mass spectrometry (HS-SPME/GC-MS). The response value of sensor W2W was significantly higher than other sensors, and its response value reached the highest on day 4. A total of 59 volatiles were detected in cut lilies by HS-SPME/GC-MS, mainly including aldehydes, alcohols, and esters. There were 19 volatiles with odor activity values (OAVs) greater than 1. Floral and fruity aromas were stronger, followed by a pungent scent. Principal component analysis (PCA) and hierarchical cluster analysis (HCA) could effectively discriminate lily samples derived from different vase times on the basis of E-nose and HS-SPME-GC-MS. In summary, our study investigates the flavor change profile and the diversity of volatile compounds during the vase period of cut lilies, and lilies on day 4 after harvest exhibited excellent aroma and flavor taking into consideration of the flavor intensity and diversity. This provided theoretical guidance for the assessment of scent volatiles and flavor quality during the vase period of cut lily flowers and will be helpful for the application of cut lilies during the postharvest process.

11.
Int J Mol Sci ; 23(9)2022 Apr 20.
Article in English | MEDLINE | ID: mdl-35562930

ABSTRACT

Nitric oxide (NO), as a ubiquitous gas signaling molecule, modulates various physiological and biochemical processes and stress responses in plants. In our study, the NO donor nitrosoglutathione (GSNO) significantly promoted tomato seedling growth under NaCl stress, whereas NO scavenger 2-(4-carboxyphenyl)-4, 4, 5, 5-tetramethylimidazoline-1-oxyl-3-oxide potassium (cPTIO) treatment reversed the positive effect of NO, indicating that NO plays an essential role in enhancing salt stress resistance. To explore the mechanism of NO-alleviated salt stress, the transcriptome of tomato leaves was analyzed. A total of 739 differentially expressed genes (DEGs) were identified and classified into different metabolic pathways, especially photosynthesis, plant hormone signal transduction, and carbon metabolism. Of these, approximately 16 and 9 DEGs involved in plant signal transduction and photosynthesis, respectively, were further studied. We found that GSNO increased the endogenous indoleacetic acid (IAA) and salicylic acid (SA) levels but decreased abscisic acid (ABA) and ethylene (ETH) levels under salt stress conditions. Additionally, GSNO induced increases in photosynthesis pigment content and chlorophyll fluorescence parameters under NaCl stress, thereby enhancing the photosynthetic capacity of tomato seedlings. Moreover, the effects of NO mentioned above were reversed by cPTIO. Together, the results of this study revealed that NO regulates the expression of genes related to phytohormone signal transduction and photosynthesis antenna proteins and, therefore, regulates endogenous hormonal equilibrium and enhances photosynthetic capacity, alleviating salt toxicity in tomato seedlings.


Subject(s)
Seedlings , Solanum lycopersicum , Solanum lycopersicum/genetics , Nitric Oxide/metabolism , Photosynthesis , Plant Growth Regulators/metabolism , Salt Stress , Seedlings/genetics , Sodium Chloride/metabolism , Sodium Chloride/pharmacology , Stress, Physiological
12.
Plants (Basel) ; 11(7)2022 Mar 30.
Article in English | MEDLINE | ID: mdl-35406914

ABSTRACT

As a gas signal molecule, hydrogen sulfide (H2S) can enhance plant stress resistance. Here, cucumber (Cucumis sativus 'Xinchun NO. 4') explants were used to investigate the role of H2S in adventitious root development under salt stress. The results show that sodium chloride (NaCl) at 10 mM produced moderate salt stress. The 100 µM sodium hydrosulfide (NaHS) treatment, a H2S donor, increased root number and root length by 38.37% and 66.75%, respectively, indicating that H2S effectively promoted the occurrence of adventitious roots in cucumber explants under salt stress. The results show that under salt stress, NaHS treatment reduced free proline content and increased the soluble sugar and soluble protein content during rooting. Meanwhile, NaHS treatment enhanced the activities of antioxidant enzymes [peroxidase (POD), superoxide dismutase (SOD), ascorbate peroxidase (APX) and catalase (CAT)], increased the content of ascorbic (ASA) and glutathione (GSH), reduced the content of hydrogen peroxide (H2O2) and the rate of superoxide radical (O2-) production, and decreased relative electrical conductivity (REC) and the content of malondialdehyde (MDA). However, the NaHS scavenger hypotaurine (HT) reversed the above effects of NaHS under salt stress. In summary, H2S promoted adventitious root development under salt stress through regulating osmotic substance content and enhancing antioxidant ability in explants.

13.
Front Microbiol ; 13: 845620, 2022.
Article in English | MEDLINE | ID: mdl-35464974

ABSTRACT

PhoPR is an important two-component signal transduction system (TCS) for microorganisms to sense and respond to phosphate limitation. Although the response regulator PhoP controls morphological development and secondary metabolism in various Streptomyces species, the function of PhoP in Actinosynnema pretiosum remains unclear. In this study, we showed that PhoP significantly represses the morphological development of the A. pretiosum X47 strain. Production of aerial mycelium and spore formation occurred much earlier in the ΔphoP strain than in X47 during growth on ISP2 medium. Transcription analysis indicated that 222 genes were differentially expressed in ∆phoP compared to strain X47. Chemotaxis genes (cheA, cheW, cheX, and cheY); flagellum biosynthesis and motility genes (flgBCDGKLN, flaD, fliD-R, motA, and swrD); and differentiation genes (whiB and ssgB) were significantly upregulated in ∆phoP. Gel-shift analysis indicated that PhoP binds to the promoters of flgB, flaD, and ssgB genes, and PHO box-like motif with the 8-bp conserved sequence GTTCACGC was identified. The transcription of phoP/phoR of X47 strain was induced at low phosphate concentration. Our results demonstrate that PhoP is a negative regulator that controls the morphological development of A. pretiosum X47 by repressing the transcription of differentiation genes.

14.
FASEB J ; 34(3): 3792-3804, 2020 03.
Article in English | MEDLINE | ID: mdl-31930567

ABSTRACT

Intercellular adhesion through homotypic interaction between cadherins regulates multiple cellular processes including cytoskeletal organization, proliferation, and survival. In this paper, we provide evidence that cadherin-11 (CDH11) binds to and promotes cell proliferation both in vitro and in vivo in synergy with the platelet-derived growth factor receptor beta (PDGFRß). Engagement of CDH11 increased the sensitivity of cells to PDGF-BB by 10- to 100-fold, resulting in rapid and sustained phosphorylation of AKT, ultimately promoting and cell proliferation and tissue regeneration. Indeed, wound healing experiments showed that healing was severely compromised in Cdh11-/- mice, as evidenced by significantly decreased proliferation, AKT phosphorylation, and extracellular matrix (ECM) synthesis of dermal cells. Our results shed light into understanding how intercellular adhesion can promote cell proliferation and may have implications for tissue regeneration and cancer progression.


Subject(s)
Cadherins/metabolism , Proto-Oncogene Proteins c-akt/metabolism , Receptor, Platelet-Derived Growth Factor beta/metabolism , Animals , Blotting, Western , Cadherins/genetics , Cell Proliferation/genetics , Cell Proliferation/physiology , Cells, Cultured , Fluorescent Antibody Technique , Humans , Immunoprecipitation , Mice , Phosphorylation/genetics , Phosphorylation/physiology , Proto-Oncogene Proteins c-akt/genetics , RNA Interference , Real-Time Polymerase Chain Reaction , Receptor, Platelet-Derived Growth Factor beta/genetics , Signal Transduction/genetics , Signal Transduction/physiology
15.
ACS Sens ; 4(7): 1816-1824, 2019 07 26.
Article in English | MEDLINE | ID: mdl-31251034

ABSTRACT

The determination of cell confluency and subculture timing for cell culture consistency is crucial in the field of cell-based research, but there is no universal standard concerning optimal confluence. In this study, gold nanodot arrays on glass substrates were used as culture substrates, and their spectral shifts of localized surface plasmon resonance (LSPR) were employed to monitor cell growth and quantify cell confluency. Experiments including cell counting, metabolic activity, focal adhesion, and cell cycle were also performed to confirm the cell growth monitoring accuracy of the LSPR signals. The LSPR signal exhibited the same trends like the increase of cell numbers and cell metabolic activity and reached the maximum as the cell growth achieved confluency, suggesting its great capability as an effective indicator to predict suitable subculture timing. The proposed sensing approach is a noninterventional, nondestructive, real-time, and useful tool to help biologists quantify the optimal subculture timing, achieve cell culture consistency, and obtain reproducible experimental results efficiently.


Subject(s)
Cell Culture Techniques/methods , Epithelial Cells/metabolism , Quantum Dots/chemistry , Actin Cytoskeleton/metabolism , Cell Count/methods , Cell Cycle/physiology , Cell Line , Cell Proliferation/physiology , Focal Adhesions/metabolism , Gold/chemistry , Gold/toxicity , Humans , Quantum Dots/toxicity , Surface Plasmon Resonance/methods
16.
J Cell Sci ; 129(15): 2950-61, 2016 08 01.
Article in English | MEDLINE | ID: mdl-27311482

ABSTRACT

We discovered that Cadherin-11 (CDH11) regulates collagen and elastin synthesis, both affecting the mechanical properties and contractile function of animal tissues. Using a Cdh11-null mouse model, we observed a significant reduction in the mechanical properties [Youngs' modulus and ultimate tensile strength (UTS)] of Cdh11(-/-) as compared to wild-type (WT) mouse tissues, such as the aorta, bladder and skin. The deterioration of mechanical properties (Youngs' modulus and UTS) was accompanied by reduced collagen and elastin content in Cdh11(-/-) mouse tissues as well as in cells in culture. Similarly, knocking down CDH11 abolished collagen and elastin synthesis in human cells, and consequently reduced their ability to generate force. Conversely, engagement of CDH11 through homophilic interactions, led to swift activation of the TGF-ß and ROCK pathways as evidenced by phosphorylation of downstream effectors. Subsequently, activation of the key transcription factors, MRTF-A (also known as MKL1) and MYOCD led to significant upregulation of collagen and elastin genes. Taken together, our results demonstrate a novel role of adherens junctions in regulating extracellular matrix (ECM) synthesis with implications for many important biological processes, including maintenance of tissue integrity, wound healing and tissue regeneration.


Subject(s)
Cadherins/metabolism , Extracellular Matrix/metabolism , Animals , Biomechanical Phenomena , Cadherins/deficiency , Collagen/genetics , Collagen/metabolism , Dermis/cytology , Elastic Modulus , Elastin/genetics , Elastin/metabolism , Fibroblasts/metabolism , Gene Knockdown Techniques , Humans , Male , Mesenchymal Stem Cells/metabolism , Mice , Models, Biological , Nuclear Proteins/metabolism , RNA, Small Interfering/metabolism , Signal Transduction , Tensile Strength , Trans-Activators/metabolism , Transforming Growth Factor beta/metabolism , rho-Associated Kinases/metabolism
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