Patel Vaishali N, Pineda Dallas L, Hoffman Matthew P
Matrix and Morphogenesis Section, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD 20892, United States.
Matrix and Morphogenesis Section, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD 20892, United States.
Matrix Biol. 2017 Jan;57-58:311-323. doi: 10.1016/j.matbio.2016.09.004. Epub 2016 Sep 6.
Branching morphogenesis is a fundamental process in the development of diverse epithelial organs such as the lung, kidney, liver, pancreas, prostate, salivary, lacrimal and mammary glands. A unifying theme during organogenesis is the importance of epithelial cell interactions with the extracellular matrix (ECM) and growth factors (GFs). The diverse developmental mechanisms giving rise to these epithelial organs involve many organ-specific GFs, but a unifying paradigm during organogenesis is the regulation of GF activity by heparan sulfates (HS) on the cell surface and in the ECM. This primarily involves the interactions of GFs with the sulfated side-chains of HS proteoglycans. HS is one of the most diverse biopolymers and modulates GF binding and signaling at the cell surface and in the ECM of all tissues. Here, we review what is known about how HS regulates branching morphogenesis of epithelial organs with emphasis on the developing salivary gland, which is a classic model to investigate epithelial-ECM interactions. We also address the structure, biosynthesis, turnover and function of HS during organogenesis. Understanding the regulatory mechanisms that control HS dynamics may aid in the development of therapeutic interventions for diseases and novel strategies for tissue engineering and regenerative medicine.
分支形态发生是多种上皮器官发育过程中的一个基本过程，这些器官包括肺、肾、肝、胰腺、前列腺、唾液腺、泪腺和乳腺等。器官发生过程中的一个共同主题是上皮细胞与细胞外基质（ECM）和生长因子（GFs）相互作用的重要性。产生这些上皮器官的多种发育机制涉及许多器官特异性生长因子，但器官发生过程中的一个统一范式是硫酸乙酰肝素（HS）在细胞表面和细胞外基质中对生长因子活性的调节。这主要涉及生长因子与硫酸乙酰肝素蛋白聚糖硫酸化侧链的相互作用。硫酸乙酰肝素是最多样化的生物聚合物之一，可调节所有组织细胞表面和细胞外基质中的生长因子结合和信号传导。在这里，我们综述了关于硫酸乙酰肝素如何调节上皮器官分支形态发生的已知内容，重点是发育中的唾液腺，它是研究上皮-细胞外基质相互作用的经典模型。我们还讨论了硫酸乙酰肝素在器官发生过程中的结构、生物合成、周转和功能。了解控制硫酸乙酰肝素动态变化的调节机制可能有助于开发针对疾病的治疗干预措施以及组织工程和再生医学的新策略。
