title: The progression of the tubulointerstitial fibrosis driven by stress-induced "proliferation-death" vicious circle.
abstract: Several hypotheses have been developed to interpret the progression of tubulointerstitial fibrosis (TF), including senescence, epithelial-mesenchymal transition, inflammation, chronic hypoxia, and reactive oxygen species. All of these hypotheses are based on persistent cell injury and localized cell death. Proliferation of neighboring renal tubular epithelial cells (RTECs) is beneficial for organ function recovery from acute injury. However, compensatory proliferation is not always advantageous, as the proliferating cells are vulnerable to ongoing detrimental stimuli, such as inflammation, endocrine stress, high blood pressure, hypoxia/ischemia, and the like. Cell injury and death promotes secretion of growth factors, which evokes proliferation of RTECs; entering the cell cycle makes the RTECs more vulnerable to injury and death. Under persistent stress, death and proliferation are mutually promoted and form the vicious circle that triggers, maintains, and augments the inflammation and progression of TF. We hypothesize that the "proliferation-death" circle is another important pathophysiologic mechanism of TF onset. Through this hypothesis, this paper interprets the development and progression of TF. Moreover, the vicious circle may be universal, underlying the development of inflammation and fibrosis in various organs and tissues. The hypothesis also suggests a potential therapy strategy for the inhibition of fibrosis.
authors.affiliation: Zhejiang Provincial Top Key Discipline in Surgery, Wenzhou Key Laboratory of Surgery, Department of Surgery, The First Affiliated Hospital, Wenzhou Medical College, Wenzhou, China.
authors.forename: Bi-cheng
authors.initials: BC
authors.lastname: Chen
authors.affiliation: Zhejiang Provincial Top Key Discipline in Surgery, Wenzhou Key Laboratory of Surgery, Department of Surgery, The First Affiliated Hospital, Wenzhou Medical College, Wenzhou, China.
authors.forename: Yong-heng
authors.initials: YH
authors.lastname: Bai
authors.affiliation: Zhejiang Provincial Top Key Discipline in Surgery, Wenzhou Key Laboratory of Surgery, Department of Surgery, The First Affiliated Hospital, Wenzhou Medical College, Wenzhou, China.
authors.forename: Li-li
authors.initials: LL
authors.lastname: Tang
authors.affiliation: Zhejiang Provincial Top Key Discipline in Surgery, Wenzhou Key Laboratory of Surgery, Department of Surgery, The First Affiliated Hospital, Wenzhou Medical College, Wenzhou, China.
authors.forename: Beng-quan
authors.initials: BQ
authors.lastname: Wang
authors.affiliation: Zhejiang Provincial Top Key Discipline in Surgery, Wenzhou Key Laboratory of Surgery, Department of Surgery, The First Affiliated Hospital, Wenzhou Medical College, Wenzhou, China.
authors.forename: Biao
authors.initials: B
authors.lastname: Liu
authors.affiliation: Transplantation Centre, The First Affiliated Hospital of Wenzhou Medical College, Wenzhou 325000, China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Cai
authors.affiliation: Transplantation Centre, The First Affiliated Hospital of Wenzhou Medical College, Wenzhou 325000, China.
authors.forename: Xia
authors.initials: X
authors.lastname: Peng
authors.affiliation: Transplantation Centre, The First Affiliated Hospital of Wenzhou Medical College, Wenzhou 325000, China. Electronic address: Bisonch@163.com.
authors.forename: Yi-rong
authors.initials: YR
authors.lastname: Yang
authors.affiliation: Transplantation Centre, The First Affiliated Hospital of Wenzhou Medical College, Wenzhou 325000, China. Electronic address: Drzhengsl@gmail.com.
authors.forename: Shao-ling
authors.initials: SL
authors.lastname: Zheng
mesh_terms: D016923:Cell Death / Q000502:physiology*; D049109:Cell Proliferation; D004847:Epithelial Cells / Q000502:physiology*; D005355:Fibrosis / Q000209:etiology / Q000503:physiopathology*; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism; D007684:Kidney Tubules / Q000473:pathology*; D009395:Nephritis, Interstitial / Q000150:complications*; D012038:Regeneration / Q000502:physiology
chemical_list: D036341:Intercellular Signaling Peptides and Proteins