Department of Zoology, Trivenidevi Bhalotia College, College Para Rd, Raniganj 713347, West Bengal, India.
Department of Physiology, University of Louisville School of Medicine, Louisville, KY 40202, USA.
Biomolecules. 2024 Sep 17;14(9):1165. doi: 10.3390/biom14091165.
The kidney is an essential excretory organ that works as a filter of toxins and metabolic by-products of the human body and maintains osmotic pressure throughout life. The kidney undergoes several physiological, morphological, and structural changes with age. As life expectancy in humans increases, cell senescence in renal aging is a growing challenge. Identifying age-related kidney disorders and their cause is one of the contemporary public health challenges. While the structural abnormalities to the extracellular matrix (ECM) occur, in part, due to changes in MMPs, EMMPRIN, and Meprin-A, a variety of epigenetic modifiers, such as DNA methylation, histone alterations, changes in small non-coding RNA, and microRNA (miRNA) expressions are proven to play pivotal roles in renal pathology. An aged kidney is vulnerable to acute injury due to ischemia-reperfusion, toxic medications, altered matrix proteins, systemic hemodynamics, etc., non-coding RNA and miRNAs play an important role in renal homeostasis, and alterations of their expressions can be considered as a good marker for AKI. Other epigenetic changes, such as histone modifications and DNA methylation, are also evident in AKI pathophysiology. The endogenous production of gaseous molecule hydrogen sulfide (HS) was documented in the early 1980s, but its ameliorative effects, especially on kidney injury, still need further research to understand its molecular mode of action in detail. HS donors heal fibrotic kidney tissues, attenuate oxidative stress, apoptosis, inflammation, and GFR, and also modulate the renin-angiotensin-aldosterone system (RAAS). In this review, we discuss the complex pathophysiological interplay in AKI and its available treatments along with future perspectives. The basic role of HS in the kidney has been summarized, and recent references and knowledge gaps are also addressed. Finally, the healing effects of HS in AKI are described with special emphasis on epigenetic regulation and matrix remodeling.
肾脏是人体重要的排泄器官，充当毒素和代谢副产物的过滤器，并在整个生命周期中维持渗透压。肾脏随着年龄的增长会发生多种生理、形态和结构变化。随着人类预期寿命的延长，肾脏老化中的细胞衰老成为一个日益严峻的挑战。识别与年龄相关的肾脏疾病及其病因是当代公共卫生挑战之一。虽然细胞外基质 (ECM) 的结构异常部分归因于 MMPs、EMMPRIN 和 Meprin-A 的变化，但多种表观遗传修饰物，如 DNA 甲基化、组蛋白改变、小非编码 RNA 和 microRNA (miRNA) 表达的改变，已被证明在肾脏病理学中发挥关键作用。衰老的肾脏易因缺血再灌注、毒性药物、基质蛋白改变、全身血液动力学等受到急性损伤，非编码 RNA 和 miRNA 在肾脏稳态中发挥重要作用，其表达的改变可作为急性肾损伤的良好标志物。其他表观遗传改变，如组蛋白修饰和 DNA 甲基化，在急性肾损伤的病理生理学中也很明显。气态分子硫化氢 (HS) 的内源性产生在 20 世纪 80 年代早期就有记载，但它的缓解作用，特别是对肾脏损伤的作用，仍需要进一步研究以详细了解其分子作用模式。HS 供体可治愈纤维化的肾脏组织，减轻氧化应激、细胞凋亡、炎症和肾小球滤过率，并调节肾素-血管紧张素-醛固酮系统 (RAAS)。在这篇综述中，我们讨论了急性肾损伤的复杂病理生理学相互作用及其现有治疗方法以及未来展望。总结了 HS 在肾脏中的基本作用，并讨论了最新参考文献和知识空白。最后，特别强调了表观遗传调控和基质重塑，描述了 HS 在急性肾损伤中的治疗作用。
