Spink7, also known as Serine Peptidase Inhibitor Kazal type 7 and ECRG2, is a gene from the SPINK family. It functions as a tumor suppressor, modulates DNA damage response, and is involved in immune defense, inflammation regulation, and maintaining epithelial barrier integrity [1]. In the DNA damage response pathway, it acts as a negative regulator of Hu-antigen R, an oncogenic RNA-binding protein. It also participates in p53-mediated apoptotic cell death [1].

In Spink7-deficient mice, they showed high susceptibility to experimental colitis, with enhanced weight loss, shorter colon length, higher disease activity index, and increased colonic tissue destruction. Neutrophils are the primary sources of Spink7 in this murine colitis model, and loss of Spink7 leads to augmented productions of multiple chemokines and cytokines [2]. In wound healing, local knockdown of Spink7 levels in wounds using siRNA gel and systemic knockout of Spink7 in KO mice resulted in delayed wound closure with sustained neutrophil infiltration, increased inflammatory responses, and elevated proteolytic activities of uPA, MMP2/9, and KLK5/7 [3].

In summary, Spink7 plays crucial roles in tumor suppression, immune defense, inflammation regulation, and maintaining epithelial integrity. Studies using Spink7-deficient mouse models have revealed its significance in colitis and wound healing, providing insights into the molecular mechanisms underlying these disease conditions and suggesting potential therapeutic targets.

References:

1. Patel, Harsh, Sheikh, M Saeed, Huang, Ying. 2024. ECRG2/SPINK7 Tumor Suppressor as Modulator of DNA Damage Response. In International journal of molecular sciences, 25, . doi:10.3390/ijms25115854. https://pubmed.ncbi.nlm.nih.gov/38892042/

2. Zhao, Na, Wang, Guojian, Long, Shuang, Su, Yongping, Wang, Tao. 2021. Neutrophils-derived Spink7 as one safeguard against experimental murine colitis. In Biochimica et biophysica acta. Molecular basis of disease, 1867, 166125. doi:10.1016/j.bbadis.2021.166125. https://pubmed.ncbi.nlm.nih.gov/33722746/

3. Zhao, Na, Wang, Guojian, Long, Shuang, Su, Yongping, Wang, Tao. . The antiprotease Spink7 promotes inflammation resolution by modulating multiple proteases activities during wound healing. In Clinical and translational medicine, 15, e70291. doi:10.1002/ctm2.70291. https://pubmed.ncbi.nlm.nih.gov/40147022/