The mechanism of PLTP on sepsis-associated acute kidney injury: some hints

Dear editor,

We appreciate the constructive comments provided by Liang and colleagues [1]. Our recent study [2] reported for the first time that PLTP is a key therapeutic target for sepsis-associated acute kidney injury (SA-AKI) in different levels. Regarding the aspects mentioned in the response above, we has been continuously and extensively investigating the mechanisms focusing PLTP in SA-AKI.

1. 1)

   Concerning the mitochondria, we have observed similar phenomena in other instances of sepsis-induced organ damage, suggesting that the protective effects of recombinant PLTP are closely linked to mitochondria. Moreover, as a member of the Tubular Lipid-binding (TULIP) superfamily, PLTP shares homology with the SMP (synaptobrevin-like, mitochondrial and peroxisomal lipid-binding protein) domain [3, 4]. The SMP domain facilitates the exchange between heterologous membranes of organelles, indicating that PLTP may play a crucial role in regulating the phospholipid composition of mitochondrial membrane. Continuous work is under way.

2. 2)

   Another article from our research team published in the Journal of Biological Chemistry (JBC) has demonstrated that PLTP in plasma is not a direct carrier of S1P, while may influence plasma S1P levels by regulating HDL metabolism [5]. However, whether PLTP affecting S1P signalling pathway in vivo remains further investigation.

3. 3)

   Concerning epigenetics mechanism, it is undeniable that post-translational modifications play a crucial role in sepsis, providing new avenues for the development of therapeutic targets and early-stage diagnosis [6, 7]. Previous studies have revealed that N-glycosylation is essential for the secretion capacity of PLTP. The site-specific removal of N-glycosylation significantly impacts both the cellular secretion of PLTP and its phospholipid transfer activity in a quantifiable manner [8, 9]. Similarly, we found that the transciptional level data and expression level data of PLTP are inconsistent in the renal tissues of CLP mice. We have also confirmed that PLTP undergoes epigenetic modifications. Currently, the relevant mechanism findings are being compiled and prepared for publication.

We are deeply grateful for the attention and support from the authors and the editorial board. Please continuous pay attention to our upcoming works.

No datasets were generated or analysed during the current study.

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Authors and Affiliations

1. Northern Jiangsu People’s Hospital Affiliated to Yangzhou University, Yangzhou, China

   Lin Song, Wei Jiang, Jiangquan Yu & Ruiqiang Zheng

2. Intensive Care Unit, Northern Jiangsu People’s Hospital, Yangzhou, China

   Lin Song, Wei Jiang, Jiangquan Yu & Ruiqiang Zheng

3. School of Laboratory Animal & Shandong Laboratory Animal Center, Shandong First Medical University & Shandong Academy of Medical Science, Jinan, Shandong, China

   Yang Yu

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Contributions

LS and WJ wrote the manuscript, YY, JQYand RQZ eventually revised the manuscript and offered perspectives. All the authors reviewed the manuscript.

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Correspondence to Ruiqiang Zheng.

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Song, L., Jiang, W., Yu, Y. et al. The mechanism of PLTP on sepsis-associated acute kidney injury: some hints. Crit Care 29, 127 (2025). https://doi.org/10.1186/s13054-025-05333-7

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• Received: 14 February 2025

• Accepted: 22 February 2025

• Published: 20 March 2025

• DOI: https://doi.org/10.1186/s13054-025-05333-7

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