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Myofibroblast in Kidney Fibrosis: Origin, Activation, and Regulation

  • Qian Yuan
  • Roderick J. Tan
  • Youhua LiuEmail author
Chapter
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 1165)

Abstract

Renal fibrosis is characterized by excessive deposition of extracellular matrix (ECM), leading to destruction of normal kidney architecture and loss of renal function. The activation of α-smooth muscle actin-positive myofibroblasts plays a key role in this process. After kidney injury, profibrotic factors are secreted by injured tubular epithelia and infiltrated inflammatory cells to promote complex cascades of signaling events leading to myofibroblastic activation, proliferation, and ECM production. The origins of myofibroblasts remain controversial, and possibilities include resident fibroblasts, pericytes, bone marrow-derived cells, and endothelial cells. Recent evidence supports the existence of localized fibrogenic niches, which provides a specialized tissue microenvironment for myofibroblastic activation and expansion. Myofibroblasts often undergo epigenetic modifications, leading to their sustained activation and resistance to apoptosis. In this chapter, we discuss the origins, heterogeneity, and activation of myofibroblasts in diseased kidneys. We also highlight novel strategies for the treatment of patients with fibrotic kidney diseases.

Keywords

Renal fibrosis Myofibroblast Fibrotic niche EMT Wnt signaling 

Notes

Acknowledgements

This work was supported by National Natural Science Foundation of China Grant 81521003 and 81770715, an American Society of Nephrology Gottschalk Award, an American Heart Association Fellow-to-Faculty award, and NIH grants DK079307, DK064005, and DK106049.

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Copyright information

© Springer Nature Singapore Pte Ltd. 2019

Authors and Affiliations

  1. 1.State Key Laboratory of Organ Failure Research, National Clinical Research Center of Kidney Disease, Division of NephrologyNanfang Hospital, Southern Medical UniversityGuangzhouChina
  2. 2.Department of MedicineUniversity of Pittsburgh School of MedicinePittsburghUSA
  3. 3.Department of PathologyUniversity of Pittsburgh School of MedicinePittsburghUSA

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