Nucleosome assembly protein 1 like 1 (NAP1L1) promotes cardiac fibrosis by inhibiting YAP1 ubiquitination and degradation.

Myocardial fibrosis post myocardial infarction (MI) is characterized by abnormal extracellular matrix (ECM) deposition and cardiac dysfunction could finally develop into serious heart disease, like heart failure. Lots of regulating factors involved in this pathological process have been reported while the specific mediators and underlying mechanisms remain to need to be further investigated. As part of the NAP1 family, Nucleosome assembly protein 1 like 1 (NAP1L1) is expressed in a wide variety of tissues. Here, we report that NAP1L1 is a significant regulator of cardiac fibrosis and is upregulated in ischemic cardiomyopathy patient hearts. Enhanced expression of NAP1L1 can promote cardiac fibroblasts (CFs) proliferation, migration, and differentiation into myofibroblasts. In contrast, loss of NAP1L1 decreased fibrosis-related mRNA and protein levels, inhibited the trans-differentiation, and blunted migration and proliferation of CFs after Transforming Growth Factorβ1（TGF-β1）stimulation. In vivo, NAP1L1 knockout mice enhanced cardiac function and reduced fibrosis area in response to MI stimuli. Mechanically, NAP1L1 binding to Yes-associated protein 1 (YAP1) protein influences its stability, and silencing NAP1L1 can inhibit YAP1 expression by promoting its ubiquitination and degradation in CFs. Collectively, NAP1L1 could potentially be a new therapeutic target for various cardiac disorders, including myocardial fibrosis.