{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,26]],"date-time":"2026-02-26T14:58:11Z","timestamp":1772117891186,"version":"3.50.1"},"reference-count":27,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2023,12,27]],"date-time":"2023-12-27T00:00:00Z","timestamp":1703635200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["febs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["FEBS Open Bio"],"published-print":{"date-parts":[[2024,2]]},"abstract":"<jats:p>Expression of \u03b1\u2010smooth muscle actin (\u03b1SMA) is constitutive in vascular smooth muscle cells, but is induced in nonmuscle cells such as hepatic stellate cells (HSCs). HSCs play important roles in both physiological homeostasis and pathological response. HSC activation is characterized by \u03b1SMA expression, which is regulated by the TGF\u03b2\u2010induced Smad pathway. Recently, protein kinase C (PKC) was identified to regulate \u03b1SMA expression. Diacylglycerol kinase (DGK) metabolizes a second\u2010messenger DG, thereby controlling components of DG\u2010mediated signaling, such as PKC. In the present study we aimed to investigate the putative role of DGK\u03b1 in \u03b1SMA expression. Use of a cellular model indicated that the DGK inhibitor R59949 promotes \u03b1SMA expression and PKC\u03b4 phosphorylation. It also facilitates Smad2 phosphorylation after 30\u2009min of TGF\u03b2 stimulation. Furthermore, immunocytochemical analysis revealed that DGK inhibitor pretreatment without TGF\u03b2 stimulation engenders \u03b1SMA expression in a granular pattern, whereas DGK inhibitor pretreatment plus TGF\u03b2 stimulation significantly induces \u03b1SMA incorporation in stress fibers. Through animal model experiments, we observed that DGK\u03b1\u2010knockout mice exhibit increased expression of \u03b1SMA in the liver after 48\u2009h of carbon tetrachloride injection, together with enhanced phosphorylation levels of Smad2 and PKC\u03b4. Together, these findings suggest that DGK\u03b1 negatively regulates \u03b1SMA expression by acting on the Smad and PKC\u03b4 signaling pathways, which differentially regulate stress fiber incorporation and protein expression of \u03b1SMA, respectively.<\/jats:p>","DOI":"10.1002\/2211-5463.13749","type":"journal-article","created":{"date-parts":[[2023,12,17]],"date-time":"2023-12-17T23:00:18Z","timestamp":1702854018000},"page":"300-308","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Ablation of\n                    <scp>DGK<\/scp>\n                    \u03b1 facilitates \u03b1\u2010smooth muscle actin expression via the Smad and\n                    <scp>PKC<\/scp>\n                    \u03b4 signaling pathways during the acute phase of\n                    <scp>\n                      CCl\n                      <sub>4<\/sub>\n                    <\/scp>\n                    \u2010induced hepatic 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