Characterization and mechanisms of microRNA-mediated paracrine signaling involving...
| Full text | |
| Author(s): Show less - |
Tanaka, Leonardo Y.
[1]
;
Araujo, Thais L. S.
[1]
;
Rodriguez, I, Andres
;
Ferraz, Mariana S.
[2]
;
Pelegati, Vitor B.
[3]
;
Morais, Mauro C. C.
[4, 5, 6]
;
dos Santos, Aline M.
[7]
;
Cesar, Carlos L.
[3]
;
Ramos, Alexandre F.
[4, 5, 6]
;
Alencar, Adriano M.
[2]
;
Laurindo, Francisco R. M.
[8]
Total Authors: 11
|
| Affiliation: | [1] Univ Sao Paulo, Sch Med, Heart Inst, Vasc Biol Lab, Sao Paulo - Brazil
[2] Univ Sao Paulo, Inst Phys, Sao Paulo - Brazil
[3] Univ Estadual Campinas, Gleb Wataghin Inst Phys, Campinas, SP - Brazil
[4] Univ Sao Paulo, Fac Med, Escola Artes Ciencias & Humanidades, Sao Paulo - Brazil
[5] Univ Sao Paulo, Fac Med, Nucleo Estudos Interdisciplinares Sistemas Comple, Dept Radiol & Oncol, Sao Paulo - Brazil
[6] Univ Sao Paulo, Fac Med, Ctr Pesquisa Translac Oncol, Inst Canc Estado Sao Paulo, Sao Paulo - Brazil
[7] Univ Estadual Campinas, Inst Biol, Dept Struct & Funct Biol, Campinas, SP - Brazil
[8] Rodriguez, Andres, I, Univ Sao Paulo, Sch Med, Heart Inst, Vasc Biol Lab, Sao Paulo - Brazil
Total Affiliations: 8
|
| Document type: | Journal article |
| Source: | AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY; v. 316, n. 3, p. H566-H579, MAR 2019. |
| Web of Science Citations: | 3 |
| Abstract | |
Although redox processes closely interplay with mechanoresponses to control vascular remodeling, redox pathways coupling mechanostimulation to cellular cytoskeletal organization remain unclear. The peri/epicellular pool of protein disulfide isomerase-A1 (pecPDIA1) supports postinjury vessel remodeling. Using distinct models, we investigated whether pecPDIA1 could work as a redox-dependent organizer of cytoskeletal mechanoresponses. In vascular smooth muscle cells (VSMCs), pecPDIA1 immunoneutralization impaired stress fiber assembly in response to equibiaxial stretch and, under uniaxial stretch, significantly perturbed cell repositioning perpendicularly to stretch orientation. During cyclic stretch, pecPDIA1 supported thiol oxidation of the known mechanosensor beta(1)-integrin and promoted polarized compartmentalization of suifenylated proteins. Using traction force microscopy, we showed that pecPDIA1 organizes intracellular force distribution. The net contractile moment ratio of platelet-derived growth factor-exposed to basal VSMCs decreased from 0.90 +/- 0.09 (IgG-exposed controls) to 0.70 +/- 0.08 after pecPDIA1 neutralization (P < 0.05), together with an enhanced coefficient of variation for distribution of force modules, suggesting increased noise. Moreover, in a single cell model, pecPDIA1 neutralization impaired migration persistence without affecting total distance or velocity, whereas siRNA-mediated total PDIA1 silencing disabled all such variables of VSMC migration. Neither expression nor total activity of the master mechanotransmitter/regulator RhoA was affected by pecPDIA1 neutralization. However, cyclic stretch-induced focal distribution of membrane-bound RhoA was disrupted by pecPDI inhibition, which promoted a nonpolarized pattern of RhoA/caveolin-3 cluster colocalization. Accordingly, FRET biosensors showed that pecPDIA1 supports localized RhoA activity at cell protrusions versus perinuclear regions. Thus. pecPDI acts as a thiol redox-dependent organizer and noise reducer mechanism of cytoskeletal repositioning, oxidant generation, and localized RhoA activation during a variety of VSMC mechanoresponses. NEW \& NOTEWORTHY Effects of a peri/epicellular pool of protein disulfide isomerase-A1 (pecPDIA1) during mechanoregulation in vascular smooth muscle cells (VSMCs) were highlighted using approaches such as equibiaxial and uniaxial stretch, random single cell migration, and traction force microscopy. pecPDIA1 regulates organization of the cytoskeleton and minimizes the noise of cell alignment, migration directionality, and persistence. pecPDIA1 mechanisms involve redox control of beta(1)-integrin and localized RhoA activation. pecPDIA1 acts as a novel organizer of mechanoadaptation responses in VSMCs. (AU) | |
| FAPESP's process: | 13/07937-8 - Redoxome - Redox Processes in Biomedicine |
| Grantee: | Ohara Augusto |
| Support type: | Research Grants - Research, Innovation and Dissemination Centers - RIDC |
| FAPESP's process: | 13/17115-5 - Epi/pericellular protein disulfide isomerase: a novel regulator of biomechanical adaptation in vascular cells |
| Grantee: | Leonardo Yuji Tanaka |
| Support type: | Scholarships in Brazil - Post-Doctorate |
| FAPESP's process: | 15/06210-2 - Grasp pathway involving on the protein disulfide isomerase externalization and its implication in endothelial cell response |
| Grantee: | Thaís Larissa Araujo de Oliveira Silva |
| Support type: | Scholarships in Brazil - Post-Doctorate |