Mitogen-activated protein kinases (MAPKs or MAP kinases) are serine-/threonine-specific protein kinases that phosphorylate substrates that control cellular functions such as proliferation, gene expression, differentiation, mitosis, survival, and apoptosis in response to various stimuli. In mammals, MAPKs comprise three subfamilies—the extracellular signal-regulated kinase (ERK) MAPKs, which are activated by growth factors and mitogens, and the c-Jun N-terminal kinase (JNK) and p38 (p38) MAPKs, which are activated by cellular stressors and inflammatory cytokines. A large body of work has explored the importance of MAPK signaling to early development and the function of stem cell populations such as embryonic stem cells,¹ skeletal muscle stem cells,² and lung stem cells.³ Given the importance of MAPKs and the specific importance of p38/MAPKs in response to several types of stress, targeting MAPK signaling pathways may represent an interesting means of supporting exogenous stem cell therapies or promoting endogenous stem cell-mediated regeneration and tissue repair in patients suffering from a range of diverse conditions. In the first of our featured articles published this month in STEM CELLS Translational Medicine, Liang et al report that ferulic acid treatment alleviates irradiation-induced impairments in skeletal stem cells (SSCs) and promotes bone regeneration through p38/MAPK and ERK/MAPK signaling pathway reactivation and so may promote bone repair following skeletal tumor treatment.⁴ In a related article published recently in STEM CELLS, Shafiquzzaman et al demonstrated, for the first time, the role of the Tak1 (mitogen-activated protein kinase kinase kinase 7)-p38/MAPK pathway in club cell regeneration and bronchiolar epithelial repair and, in doing so, highlighted a potential therapeutic target for bronchiole-related disorders.⁵

The platelet-derived growth factor (PDGF) family primarily regulates the growth and division of mesenchymal cells such as fibroblasts and smooth muscle cells. The four polypeptide chains encoded by the PDGFA, PDGFB, PDGFC, and PDGFD genes form five different dimeric glycoproteins: PDGF-AA, -BB, -AB, -CC, and -DD. The binding of PDGFs to receptors that possess differential binding affinities induces the dimerization of PDGFR-α and -β chain isoforms to form homodimeric and heterodimeric receptors and the activation of receptor tyrosine kinase activity. PDGFR activation stimulates a range of crucial intracellular signaling pathways that promote cell proliferation and migration⁶ and plays essential roles during embryogenesis, controlling the development of the lungs, intestines, skin, testis, kidneys, hematopoietic system, and blood vessels. While PDGF also plays a vital role in wound healing in later life,⁷ PDGF signaling can contribute to the development of cancer, inflammatory disease, pulmonary fibrosis, atherosclerosis, asthma, and chronic obstructive pulmonary disease.⁸ In the second of our featured articles published this month in STEM CELLS Translational Medicine, Shaw et al explore how aging and injury impact the responses of kidney mesenchymal cells through a detailed analysis of marker protein/gene expression, which includes the specific expression of PDGFR-α and PDGFR-β by renal myofibroblasts.⁹ In a related article published recently in STEM CELLS, Zhou et al reported on how synergistic interactions between mesenchymal stem cells (MSCs) and endothelial cells could improve bone regeneration and how the differentiation of MSCs into pericytes through the PDGF-BB/PDGFR-β signaling pathway supported blood vessel formation.¹⁰

丝裂原活化蛋白激酶（MAPK 或 MAP 激酶）是丝氨酸/苏氨酸特异性蛋白激酶，可磷酸化控制细胞功能（如增殖、基因表达、分化、有丝分裂、存活和细胞凋亡）的底物以响应各种刺激。在哺乳动物中，MAPK 包括三个亚家族——细胞外信号调节激酶 (ERK) MAPK，它们由生长因子和有丝分裂原激活，以及 c-Jun N 末端激酶 (JNK) 和 p38 (p38) MAPK，它们被激活由细胞压力源和炎性细胞因子引起。大量工作探索了 MAPK 信号传导对早期发育和干细胞群（如胚胎干细胞、¹骨骼肌干细胞、²和肺干细胞）功能的重要性。³鉴于 MAPKs 的重要性以及 p38/MAPKs 在应对多种压力方面的特殊重要性，靶向 MAPK 信号通路可能代表一种有趣的方式来支持外源性干细胞疗法或促进内源性干细胞介导的再生和组织修复。从一系列不同的条件。在本月发表在STEM CELLS Translational Medicine 上的第一篇专题文章中，Liang 等人报告说，阿魏酸治疗可减轻辐射诱导的骨骼干细胞 (SSC) 损伤，并通过 p38/MAPK 和 ERK/MAPK 信号通路促进骨再生再激活等可能促进骨骼肿瘤治疗后的骨修复。⁴在最近发表的一篇相关文章中STEM CELLS、Shafiquzzaman 等人首次证明了 Tak1（丝裂原活化蛋白激酶激酶 7）-p38/MAPK 通路在棒状细胞再生和细支气管上皮修复中的作用，并在此过程中强调了潜在的细支气管相关疾病的治疗靶点。⁵

血小板衍生生长因子 (PDGF) 家族主要调节间充质细胞（如成纤维细胞和平滑肌细胞）的生长和分裂。由PDGFA、PDGFB、PDGFC和PDGFD基因编码的四个多肽链形成五种不同的二聚糖蛋白：PDGF-AA、-BB、-AB、-CC 和 -DD。PDGFs 与具有不同结合亲和力的受体的结合诱导 PDGFR-α 和 -β 链同种型的二聚化，形成同二聚体和异二聚体受体，并激活受体酪氨酸激酶活性。PDGFR 激活刺激了一系列促进细胞增殖和迁移的关键细胞内信号通路⁶并在胚胎发生过程中发挥重要作用，控制肺、肠、皮肤、睾丸、肾脏、造血系统和血管的发育。虽然 PDGF 在晚年的伤口愈合中也起着至关重要的作用，但⁷ PDGF 信号传导可促进癌症、炎症性疾病、肺纤维化、动脉粥样硬化、哮喘和慢性阻塞性肺病的发展。⁸在我们本月发表在STEM CELLS Translational Medicine 上的第二篇专题文章中，Shaw 等人通过对标记蛋白/基因表达的详细分析（包括 PDGFR 的特异性表达）探讨了衰老和损伤如何影响肾间充质细胞的反应-α 和 PDGFR-β 由肾肌成纤维细胞产生。⁹在最近发表在STEM CELLS 上的一篇相关文章中，Zhou 等人报道了间充质干细胞 (MSCs) 和内皮细胞之间的协同相互作用如何促进骨再生，以及 MSCs 如何通过 PDGF-BB/PDGFR-β 信号传导分化为周细胞通路支持血管形成。¹⁰