Lung Myofibroblasts Promote Macrophage Profibrotic Activity through Lactate-induced Histone Lactylation

Cui, Huachun; Xie, Na; Banerjee, Sami; Ge, Jing; Jiang, Dechun; Dey, Tushar Kanti; Matthews, Qiana L.; Liu, Rui-Ming; Liu, Gang

doi:10.1165/rcmb.2020-0360oc

Cited by 157 publications

(139 citation statements)

References 48 publications

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“…Evidence has shown that inflammatory macrophages undergo aerobic glycolysis to generate lactic acid following toll-like receptor stimulation, and then the lactic acids bind to lysine residues in the histone tails, referred to as histone lactylation, which participates in the transformation process of macrophages from M1 to M2 to restore normal cellular functions [ 134 ]. In the pathogenesis of pulmonary fibrosis, lactic acid induced histone lactylation in the promoter of the prefibrotic gene in macrophages, which is mediated by P300 [ 135 ]. In addition to binding to histones, lactylation can also occur on the sites of nonhistones.…”

Section: The Main Types Of Mitochondrial Ptms In Cardiovascular DImentioning

confidence: 99%

[Retracted] The Role of Posttranslational Modification and Mitochondrial Quality Control in Cardiovascular Diseases

Liu

Zhong

Guo

2021

Oxidative Medicine and Cellular Longevity

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Cardiovascular disease (CVD) is the leading cause of death in the world. The mechanism behind CVDs has been studied for decades; however, the pathogenesis is still controversial. Mitochondrial homeostasis plays an essential role in maintaining the normal function of the cardiovascular system. The alterations of any protein function in mitochondria may induce abnormal mitochondrial quality control and unexpected mitochondrial dysfunction, leading to CVDs. Posttranslational modifications (PTMs) affect protein function by reversibly changing their conformation. This review summarizes how common and novel PTMs influence the development of CVDs by regulating mitochondrial quality control. It provides not only ideas for future research on the mechanism of some types of CVDs but also ideas for CVD treatments with therapeutic potential.

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Section: The Main Types Of Mitochondrial Ptms In Cardiovascular DImentioning

confidence: 99%

[Retracted] The Role of Posttranslational Modification and Mitochondrial Quality Control in Cardiovascular Diseases

Liu

Zhong

Guo

2021

Oxidative Medicine and Cellular Longevity

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“…The report suggested that lactate modulates metabolic-alteration-related gene expression through histone H3 Kla in mouse macrophages (Zhang et al, 2019). Later studies have also reported the key roles of lactate-induced Kla in macrophages in the transition from a pro-inflammatory state to a reparative state (Irizarry-Caro et al, 2020) and the pathogenesis of lung fibrosis (Cui et al, 2021). However, it has not been elucidated whether Kla occurs and is regulated by exogenous lactate treatment or by stimulation that increases endogenous lactate levels in other types of cells/tissues, including brain cells.…”

Section: Introductionmentioning

confidence: 98%

Protein lactylation induced by neural excitation

et al. 2021

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Lactate has diverse roles in the brain at the molecular and behavioral levels under physiological and pathophysiological conditions. This study investigates whether lysine lactylation (Kla), a lactate-derived posttranslational modification in macrophages, occurs in brain cells and if it does, whether Kla is induced by the stimuli that accompany changes in lactate levels. Here, we show that Kla in brain cells is regulated by neural excitation and social stress, with parallel changes in lactate levels. These stimuli increase Kla, which is associated with the expression of the neuronal activity marker c-Fos, as well as with decreased social behavior and increased anxiety-like behavior in the stress model. In addition, we identify 63 candidate lysine-lactylated proteins and find that stress preferentially increases histone H1 Kla. This study may open an avenue for the exploration of a role of neuronal activity-induced lactate mediated by protein lactylation in the brain.

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“…In the lungs of pulmonary fibrosis mice treated with bleomycin and humans with idiopathic pulmonary fibrosis, histone lactylation was increased. Histone lactylation at the promoter-proximal regions of reparative genes such as Arg1, platelet-derived growth factor (Pdgf), thrombospondin 1 (Thbs1), and Vegf was significantly increased in lactate-treated macrophages (84).…”

Section: Lactylation In Fibrosismentioning

confidence: 99%

“…Further, lactyl-CoA has been detected by liquid chromatography mass spectrometry in mammalian cells and tissues (95). Elucidation of the biochemistry involved in both the transfer of lactyl moieties from lactyl-CoA to histones through p300 or other writer enzymes (79,84) and the removal of lactyl groups in cellular physiology is an ongoing effort. Similarly, the readers of lysine lactylation that result in cellular changes remain to be identified (Figure 2).…”

Section: Perspectives Readers Writers and Erasersmentioning

confidence: 99%

Lactylation, a Novel Metabolic Reprogramming Code: Current Status and Prospects

et al. 2021

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Lactate is an end product of glycolysis. As a critical energy source for mitochondrial respiration, lactate also acts as a precursor of gluconeogenesis and a signaling molecule. We briefly summarize emerging concepts regarding lactate metabolism, such as the lactate shuttle, lactate homeostasis, and lactate-microenvironment interaction. Accumulating evidence indicates that lactate-mediated reprogramming of immune cells and enhancement of cellular plasticity contribute to establishing disease-specific immunity status. However, the mechanisms by which changes in lactate states influence the establishment of diverse functional adaptive states are largely uncharacterized. Posttranslational histone modifications create a code that functions as a key sensor of metabolism and are responsible for transducing metabolic changes into stable gene expression patterns. In this review, we describe the recent advances in a novel lactate-induced histone modification, histone lysine lactylation. These observations support the idea that epigenetic reprogramming-linked lactate input is related to disease state outputs, such as cancer progression and drug resistance.

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Lung Myofibroblasts Promote Macrophage Profibrotic Activity through Lactate-induced Histone Lactylation

Cited by 157 publications

References 48 publications

[Retracted] The Role of Posttranslational Modification and Mitochondrial Quality Control in Cardiovascular Diseases

[Retracted] The Role of Posttranslational Modification and Mitochondrial Quality Control in Cardiovascular Diseases

Protein lactylation induced by neural excitation

Lactylation, a Novel Metabolic Reprogramming Code: Current Status and Prospects

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