类有机物
肾
肾素-血管紧张素系统
内分泌学
平衡
生物
医学
内科学
细胞生物学
血压
作者
Anusha S. Shankar,Zhaoyu Du,Hector Tejeda-Mora,Thierry P P van den Bosch,Sander S. Korevaar,Ingrid M. van den Berg-Garrelds,Eric M. Bindels,Carmen López‐Iglesias,Marian C. Clahsen-van Groningen,Joost Gribnau,Carla C. Baan,A.H. Jan Danser,Ewout J. Hoorn,Martin J. Hoogduijn
标识
DOI:10.1016/j.kint.2020.08.008
摘要
Renin production by the kidney is of vital importance for salt, volume, and blood pressure homeostasis. The lack of human models hampers investigation into the regulation of renin and its relevance for kidney physiology. To develop such a model, we used human induced pluripotent stem cell–derived kidney organoids to study the role of renin and the renin-angiotensin system in the kidney. Extensive characterization of the kidney organoids revealed kidney-specific cell populations consisting of podocytes, proximal and distal tubular cells, stromal cells and endothelial cells. We examined the presence of various components of the renin-angiotensin system such as angiotensin II receptors, angiotensinogen, and angiotensin-converting enzymes 1 and 2. We identified by single-cell sequencing, immunohistochemistry, and functional assays that cyclic AMP stimulation induces a subset of pericytes to increase the synthesis and secretion of enzymatically active renin. Renin production by the organoids was responsive to regulation by parathyroid hormone. Subcutaneously implanted kidney organoids in immunodeficient IL2Ry-/-Rag2-/- mice were successfully vascularized, maintained tubular and glomerular structures, and retained capacity to produce renin two months after implantation. Thus, our results demonstrate that kidney organoids express renin and provide insights into the endocrine potential of human kidney organoids, which is important for regenerative medicine in the context of the endocrine system.
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