School of Life Science and Technology, Key Laboratory of Developmental Genes and Human Disease, Southeast University, Nanjing, China.
Zebrafish Centre for Advanced Drug Discovery, Keenan Research Centre for Biomedical Science, St. Michael's Hospital, Li Ka Shing Knowledge Institute, Toronto, Ontario, Canada.
J Cell Physiol. 2021 May;236(5):3700-3709. doi: 10.1002/jcp.30106. Epub 2020 Oct 14.
Cardiac hypertrophy is a compensatory response to pathological stimuli, ultimately progresses to cardiomyopathy, heart failure, or sudden death. Although many signaling pathways have been reported to be involved in the hypertrophic process, it is still not fully clear about the underlying molecular mechanisms for cardiac hypertrophy. Hedgehog acyltransferase-like (Hhatl), a sarcoplasmic reticulum-resident protein, exhibits high expression in the heart and muscle. However, the biological role of Hhatl in the heart remains unknown. In this study, we first found that the expression level of Hhatl is markedly decreased in cardiac hypertrophy. We further studied the role of hhatla, homolog of Hhatl with the zebrafish model. The depletion of hhatla in zebrafish leads to cardiac defects, as well as an enhanced level of hypertrophic markers. Besides, we found that calcineurin signaling participates in hhatla depletion-induced cardiac hypertrophy. Together, these results demonstrate a critical role for hhatla in cardiac hypertrophy.
心肌肥厚是对病理性刺激的代偿反应，最终进展为心肌病、心力衰竭或心源性猝死。尽管已经报道了许多信号通路参与了肥厚过程，但心肌肥厚的潜在分子机制仍不完全清楚。Hedgehog 酰基转移酶样（Hhatl）是一种肌浆网驻留蛋白，在心脏和肌肉中表达水平较高。然而，Hhatl 在心脏中的生物学作用尚不清楚。在这项研究中，我们首先发现 Hhatl 的表达水平在心肥大中显著降低。我们进一步研究了 hhatla 的作用，hhatla 是 Hhatl 的斑马鱼同源物。在斑马鱼中敲低 hhatla 会导致心脏缺陷，并增加肥厚标志物的水平。此外，我们发现钙调神经磷酸酶信号参与了 hhatla 敲低诱导的心肌肥厚。综上所述，这些结果表明 hhatla 在心肌肥厚中起着关键作用。
