TY - JOUR
T1 - The role of extracellular matrix stiffness in regulating cytoskeletal remodeling via vinculin in synthetic smooth muscle cells
AU - Shen, Kai
AU - Kenche, Harshavardhan
AU - Zhao, Hua
AU - Li, Jinping
AU - Stone, Jasimine
N1 - Publisher Copyright:
© 2018 Elsevier Inc.
PY - 2019/1/1
Y1 - 2019/1/1
N2 - Vinculin is a key player in sensing and responding to external mechanical cues such as extracellular matrix stiffness. Increased matrix stiffness is often associated with certain pathological conditions including hypertension induced cellular cytoskeleton changes in vascular smooth muscle (VSM) cells. However, little is known on how stiffness affects cytoskeletal remodeling via vinculin in VSM cells. Thus, we utilized matrices with elastic moduli that simulate vascular stiffness in different stages of hypertension to investigate how matrix stiffness regulates cell cytoskeleton via vinculin in synthetic VSM cells. Through selecting a suitable reference gene, we found that an increase in physiologically relevant extracellular matrix stiffness (2–50 kPa) downregulates vinculin gene expression but upregulates vinculin protein expression. This discrepancy, which was not observed previously for non-muscle cells, suggests that the vinculin-mediated mecahnotransduction mechanism in synthetic VSM cells may be more complex than those proposed for non-muscle cells. Also adding to previous findings, we found that VSM cell growth may be impeded by substrates that are either too soft or too rigid.
AB - Vinculin is a key player in sensing and responding to external mechanical cues such as extracellular matrix stiffness. Increased matrix stiffness is often associated with certain pathological conditions including hypertension induced cellular cytoskeleton changes in vascular smooth muscle (VSM) cells. However, little is known on how stiffness affects cytoskeletal remodeling via vinculin in VSM cells. Thus, we utilized matrices with elastic moduli that simulate vascular stiffness in different stages of hypertension to investigate how matrix stiffness regulates cell cytoskeleton via vinculin in synthetic VSM cells. Through selecting a suitable reference gene, we found that an increase in physiologically relevant extracellular matrix stiffness (2–50 kPa) downregulates vinculin gene expression but upregulates vinculin protein expression. This discrepancy, which was not observed previously for non-muscle cells, suggests that the vinculin-mediated mecahnotransduction mechanism in synthetic VSM cells may be more complex than those proposed for non-muscle cells. Also adding to previous findings, we found that VSM cell growth may be impeded by substrates that are either too soft or too rigid.
KW - Extracellular matrix
KW - Stiffness
KW - Synthetic vascular smooth muscle cells
KW - Vinculin
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U2 - 10.1016/j.bbrc.2018.11.142
DO - 10.1016/j.bbrc.2018.11.142
M3 - Article
C2 - 30502091
AN - SCOPUS:85057150481
SN - 0006-291X
VL - 508
SP - 302
EP - 307
JO - Biochemical and Biophysical Research Communications
JF - Biochemical and Biophysical Research Communications
IS - 1
ER -