{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n HSPA12B is an atypical member of the HSP70 family that is primarily expressed in endothelial cells and other tissues, where it plays multifunctional protective roles under diverse pathological conditions. Its expression is induced during angiogenic and ischemic challenges, and in several experimental models overexpression of HSPA12B preserves endothelial integrity, promotes capillary formation, and enhances tissue perfusion in myocardial infarction, ischemia/reperfusion injury, and hind‐limb or cerebral ischemia – effects that are mediated, at least in part, via activation of PI3K/Akt–eNOS or PI3K/Akt/mTOR signaling and interactions with transcriptional regulators such as YAP/TEAD4."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "6"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n In models of inflammatory and septic injury, HSPA12B attenuates endothelial barrier disruption, decreases leukocyte adhesion and cytokine release, and thus mitigates tissue damage. Moreover, both intracellular and extracellular HSPA12B levels correlate with improved survival and reduced organ injury in sepsis, implicating it as both an effector and potential biomarker."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "7", "end_ref": "10"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Post‐transcriptional regulators such as microRNAs (e.g., miR‑134 and miR‑4505) negatively modulate HSPA12B expression, which in turn impairs its cytoprotective effects in neuronal and endothelial cells during ischemic and endotoxin-induced injury."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "11"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n In the oncological context, dysregulation of HSPA12B is associated with tumor progression and drug resistance. For instance, its overexpression can promote lung tumor growth via a cyclooxygenase‑2–dependent mechanism and contribute to cell adhesion–mediated drug resistance in non‑Hodgkin’s lymphoma, whereas in colorectal and colon cancers reduced HSPA12B expression is observed, and its regulation by miRNAs can modulate the sensitivity of cancer cells to chemotherapeutic agents."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "12", "end_ref": "15"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Additional studies have highlighted roles for HSPA12B in neuroinflammatory processes and developmental contexts, with altered expression observed in conditions such as schizophrenia and atherosclerosis"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "16"}]}, {"type": "t", "text": "and"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "17"}]}, {"type": "t", "text": ", while in invertebrates, interaction of HSPA12B with Cry toxins has been linked to insect resistance."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "18"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Overall, HSPA12B functions as a stress-inducible chaperone that not only safeguards endothelial and neuronal cells by modulating apoptosis, inflammation, and angiogenesis but also influences tumor behavior and drug response. These diverse roles establish HSPA12B as a promising therapeutic target and potential biomarker in cardiovascular, neurological, inflammatory, and oncological diseases.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Jingjin Li, Yangyang Zhang, Chuanfu Li, et al. "}, {"type": "b", "children": [{"type": "t", "text": "HSPA12B attenuates cardiac dysfunction and remodelling after myocardial infarction through an eNOS-dependent mechanism."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cardiovasc Res (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/cvr/cvt139"}], "href": "https://doi.org/10.1093/cvr/cvt139"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23729663"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23729663"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Qiuyue Kong, Leyang Dai, Yana Wang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "HSPA12B Attenuated Acute Myocardial Ischemia/reperfusion Injury via Maintaining Endothelial Integrity in a PI3K/Akt/mTOR-dependent Mechanism."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Sci Rep (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/srep33636"}], "href": "https://doi.org/10.1038/srep33636"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27644317"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27644317"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Yujie Ma, Chen Lu, Chuanfu Li, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Overexpression of HSPA12B protects against cerebral ischemia/reperfusion injury via a PI3K/Akt-dependent mechanism."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochim Biophys Acta (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.bbadis.2012.10.003"}], "href": "https://doi.org/10.1016/j.bbadis.2012.10.003"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23046810"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23046810"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "W Chi, F Meng, Y Li, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Downregulation of miRNA-134 protects neural cells against ischemic injury in N2A cells and mouse brain with ischemic stroke by targeting HSPA12B."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Neuroscience (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.neuroscience.2014.06.062"}], "href": "https://doi.org/10.1016/j.neuroscience.2014.06.062"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25003713"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25003713"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Wenying Chi, Fanjun Meng, Yan Li, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Impact of microRNA-134 on neural cell survival against ischemic injury in primary cultured neuronal cells and mouse brain with ischemic stroke by targeting HSPA12B."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Brain Res (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.brainres.2014.09.072"}], "href": "https://doi.org/10.1016/j.brainres.2014.09.072"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25304362"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25304362"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Yanlin Zhao, Chang Liu, Jiali Liu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "HSPA12B promotes functional recovery after ischaemic stroke through an eNOS-dependent mechanism."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Cell Mol Med (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1111/jcmm.13507"}], "href": "https://doi.org/10.1111/jcmm.13507"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "29411514"}], "href": "https://pubmed.ncbi.nlm.nih.gov/29411514"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Jun Wu, Xuehan Li, Lei Huang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "HSPA12B inhibits lipopolysaccharide-induced inflammatory response in human umbilical vein endothelial cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Cell Mol Med (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1111/jcmm.12464"}], "href": "https://doi.org/10.1111/jcmm.12464"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25545050"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25545050"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Qiuxiang Kang, Yi Chen, Xu Zhang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Heat shock protein A12B protects against sepsis-induced impairment in vascular endothelial permeability."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Surg Res (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.jss.2015.12.034"}], "href": "https://doi.org/10.1016/j.jss.2015.12.034"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27083952"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27083952"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "Xiaojin Zhang, Jingjin Li, Chuanfu Li, et al. "}, {"type": "b", "children": [{"type": "t", "text": "HSPA12B attenuates acute lung injury during endotoxemia in mice."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Int Immunopharmacol (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.intimp.2015.09.022"}], "href": "https://doi.org/10.1016/j.intimp.2015.09.022"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26428851"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26428851"}]}, {"type": "r", "ref": 10, "children": [{"type": "t", "text": "Ran Zhang, Xiao-jian Wan, Xu Zhang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Plasma HSPA12B is a potential predictor for poor outcome in severe sepsis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "PLoS One (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1371/journal.pone.0101215"}], "href": "https://doi.org/10.1371/journal.pone.0101215"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24977412"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24977412"}]}, {"type": "r", "ref": 11, "children": [{"type": "t", "text": "Xu Zhang, Yi Chen, Lei Wang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "MiR-4505 aggravates lipopolysaccharide-induced vascular endothelial injury by targeting heat shock protein A12B."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Med Rep (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.3892/mmr.2017.7936"}], "href": "https://doi.org/10.3892/mmr.2017.7936"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "29115487"}], "href": "https://pubmed.ncbi.nlm.nih.gov/29115487"}]}, {"type": "r", "ref": 12, "children": [{"type": "t", "text": "He Ma, Ting Lu, Xiaojin Zhang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "HSPA12B: a novel facilitator of lung tumor growth."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Oncotarget (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.18632/oncotarget.3533"}], "href": "https://doi.org/10.18632/oncotarget.3533"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25909170"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25909170"}]}, {"type": "r", "ref": 13, "children": [{"type": "t", "text": "Yuejiao Huang, Chunlei Peng, Jie Tang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The expression of heat shock protein A12B (HSPA12B) in non-Hodgkin's lymphomas."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Ann Transl Med (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.21037/atm-21-4185"}], "href": "https://doi.org/10.21037/atm-21-4185"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "34734014"}], "href": "https://pubmed.ncbi.nlm.nih.gov/34734014"}]}, {"type": "r", "ref": 14, "children": [{"type": "t", "text": "Jingjie Zhou, Aiping Zhang, Liang Fan "}, {"type": "b", "children": [{"type": "t", "text": "HSPA12B Secreted by Tumor-Associated Endothelial Cells Might Induce M2 Polarization of Macrophages via Activating PI3K/Akt/mTOR Signaling."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Onco Targets Ther (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.2147/OTT.S254985"}], "href": "https://doi.org/10.2147/OTT.S254985"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "32982299"}], "href": "https://pubmed.ncbi.nlm.nih.gov/32982299"}]}, {"type": "r", "ref": 15, "children": [{"type": "t", "text": "Li Zhang, Heping Chen, Yueqiong Song, et al. "}, {"type": "b", "children": [{"type": "t", "text": "MiR-325 Promotes Oxaliplatin-Induced Cytotoxicity Against Colorectal Cancer Through the HSPA12B/PI3K/AKT/Bcl-2 Pathway."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Dig Dis Sci (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s10620-020-06579-7"}], "href": "https://doi.org/10.1007/s10620-020-06579-7"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "32914380"}], "href": "https://pubmed.ncbi.nlm.nih.gov/32914380"}]}, {"type": "r", "ref": 16, "children": [{"type": "t", "text": "Julie L Pongrac, Frank A Middleton, Lansha Peng, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Heat shock protein 12A shows reduced expression in the prefrontal cortex of subjects with schizophrenia."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biol Psychiatry (2004)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.biopsych.2004.09.005"}], "href": "https://doi.org/10.1016/j.biopsych.2004.09.005"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15601604"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15601604"}]}, {"type": "r", "ref": 17, "children": [{"type": "t", "text": "Zhihua Han, Quynh A Truong, Shirley Park, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Two Hsp70 family members expressed in atherosclerotic lesions."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Proc Natl Acad Sci U S A (2003)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1073/pnas.252764399"}], "href": "https://doi.org/10.1073/pnas.252764399"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12552099"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12552099"}]}, {"type": "r", "ref": 18, "children": [{"type": "t", "text": "Lina Xu, Natalie Ferry, Zhenying Wang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "A proteomic approach to study the mechanism of tolerance to Bt toxins in Ostrinia furnacalis larvae selected for resistance to Cry1Ab."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Transgenic Res (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s11248-013-9718-3"}], "href": "https://doi.org/10.1007/s11248-013-9718-3"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23748999"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23748999"}]}]}]}