Pstpip2, or Proline-serine-threonine-phosphatase-interacting protein 2, belongs to the F-BAR domain family. It exhibits lipid-binding, membrane deformation, and F-actin binding activity, playing important roles at the membrane-cytoskeleton interface. It is involved in macrophage activation, neutrophil migration, cytokine production, and osteoclast differentiation, and has been linked to innate immune and autoinflammatory diseases [1].

In AAN mouse models, conditional knock-in of Pstpip2 in kidneys inhibited cell apoptosis, reduced neutrophil infiltration, and alleviated kidney injury, while down-regulation of Pstpip2 promoted kidney damage. The mechanism involves Pstpip2 affecting NET formation by regulating IL-19 expression via inhibition of NF-κB pathway activation in renal tubular epithelial cells [2]. In alcoholic liver injury, both in vivo and in vitro models showed that decreasing Pstpip2 expression was observed. Overexpressing Pstpip2 protected against liver parenchymal distortion and curbed caspase-dependent hepatocyte apoptosis, and the STAT3 pathway was identified as a direct signaling pathway regulated by Pstpip2 [3]. In AIA rats, AAV-mediated overexpression of Pstpip2 before arthritis onset significantly reduced the severity of AIA, along with decreased inflammatory responses and osteoclast numbers [4].

In conclusion, Pstpip2 plays crucial roles in multiple biological processes related to inflammation and cell apoptosis. Gene-knockout or conditional-knockout mouse models have revealed its significance in diseases such as aristolochic acid nephropathy, alcoholic liver injury, and adjuvant-induced arthritis, suggesting it could be a potential therapeutic target for these and other related inflammatory diseases.

References:

1. Xu, Jie-Jie, Li, Hai-Di, Du, Xiao-Sa, Huang, Cheng, Li, Jun. 2021. Role of the F-BAR Family Member PSTPIP2 in Autoinflammatory Diseases. In Frontiers in immunology, 12, 585412. doi:10.3389/fimmu.2021.585412. https://pubmed.ncbi.nlm.nih.gov/34262554/

2. Du, Changlin, Xu, Chuanting, Jia, Pengcheng, Huang, Cheng, Ma, Taotao. 2024. PSTPIP2 ameliorates aristolochic acid nephropathy by suppressing interleukin-19-mediated neutrophil extracellular trap formation. In eLife, 13, . doi:10.7554/eLife.89740. https://pubmed.ncbi.nlm.nih.gov/38314821/

3. Yin, Na-Na, Chen, Xin, Sun, Ying-Yin, Huang, Cheng, Li, Jun. 2024. PSTPIP2 protects against alcoholic liver injury and invokes STAT3-mediated suppression of apoptosis. In Biochemical pharmacology, 225, 116334. doi:10.1016/j.bcp.2024.116334. https://pubmed.ncbi.nlm.nih.gov/38824967/

4. Yao, Yao, Cai, Xiaoyu, Yu, Haixia, Huang, Cheng, Li, Jun. 2019. PSTPIP2 attenuates joint damage and suppresses inflammation in adjuvant-induced arthritis. In European journal of pharmacology, 859, 172558. doi:10.1016/j.ejphar.2019.172558. https://pubmed.ncbi.nlm.nih.gov/31325437/