TY - JOUR
T1 - Fibroblast-Specific Depletion of Human Antigen R Alleviates Myocardial Fibrosis Induced by Cardiac Stress
AU - Patil, Mallikarjun
AU - Singh, Sarojini
AU - Dubey, Praveen Kumar
AU - Tousif, Sultan
AU - Umbarkar, Prachi
AU - Zhang, Qinkun
AU - Lal, Hind
AU - Sewell-Loftin, Mary Kathryn
AU - Umeshappa, Channakeshava Sokke
AU - Ghebre, Yohannes T.
AU - Pogwizd, Steven
AU - Zhang, Jianyi
AU - Krishnamurthy, Prasanna
N1 - Publisher Copyright:
© 2024 The Authors
PY - 2024/6
Y1 - 2024/6
N2 - Cardiac fibrosis can be mitigated by limiting fibroblast-to-myofibroblast differentiation and proliferation. Human antigen R (HuR) modulates messenger RNA stability and expression of multiple genes. However, the direct role of cardiac myofibroblast HuR is unknown. Myofibroblast-specific deletion of HuR limited cardiac fibrosis and preserved cardiac functions in pressure overload injury. Knockdown of HuR in transforming growth factor-β1–treated cardiac fibroblasts suppressed myofibroblast differentiation and proliferation. HuR deletion abrogated the expression and messenger RNA stability of cyclins D1 and A2, suggesting a potential mechanism by which HuR promotes myofibroblast proliferation. Overall, these data suggest that inhibition of HuR could be a potential therapeutic approach to limit cardiac fibrosis.
AB - Cardiac fibrosis can be mitigated by limiting fibroblast-to-myofibroblast differentiation and proliferation. Human antigen R (HuR) modulates messenger RNA stability and expression of multiple genes. However, the direct role of cardiac myofibroblast HuR is unknown. Myofibroblast-specific deletion of HuR limited cardiac fibrosis and preserved cardiac functions in pressure overload injury. Knockdown of HuR in transforming growth factor-β1–treated cardiac fibroblasts suppressed myofibroblast differentiation and proliferation. HuR deletion abrogated the expression and messenger RNA stability of cyclins D1 and A2, suggesting a potential mechanism by which HuR promotes myofibroblast proliferation. Overall, these data suggest that inhibition of HuR could be a potential therapeutic approach to limit cardiac fibrosis.
KW - cardiac fibrosis
KW - heart failure
KW - human antigen R
KW - left ventricular remodeling
KW - myofibroblasts
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U2 - 10.1016/j.jacbts.2024.03.004
DO - 10.1016/j.jacbts.2024.03.004
M3 - Article
AN - SCOPUS:85195181817
SN - 2452-302X
VL - 9
SP - 754
EP - 770
JO - JACC: Basic to Translational Science
JF - JACC: Basic to Translational Science
IS - 6
ER -