The effects of intrinsic apoptosis on cystogenesis in PKD1-deficient ADPKD pig model

Runming Wang; Wenya Li; Suhong Zhang; Ya Song; Haiting Dai; Tan Tan; Xiaoxiang Hu; Yiming Xing

doi:10.1016/j.gene.2021.145792

The effects of intrinsic apoptosis on cystogenesis in PKD1-deficient ADPKD pig model

Gene. 2021 Sep 25:798:145792. doi: 10.1016/j.gene.2021.145792. Epub 2021 Jun 25.

Authors

Runming Wang¹, Wenya Li¹, Suhong Zhang¹, Ya Song¹, Haiting Dai¹, Tan Tan², Xiaoxiang Hu³, Yiming Xing⁴

Affiliations

¹ College of Biological Sciences, State Key Laboratory for Agrobiotechnology, China Agricultural University, Beijing, PR China.
² College of Animal Science and Technology, China Agricultural University, Beijing, PR China.
³ College of Biological Sciences, State Key Laboratory for Agrobiotechnology, China Agricultural University, Beijing, PR China; National Engineering Laboratory for Animal Breeding, China Agricultural University, Beijing, PR China.
⁴ College of Biological Sciences, State Key Laboratory for Agrobiotechnology, China Agricultural University, Beijing, PR China. Electronic address: ymxing@cau.edu.cn.

PMID: 34175399
DOI: 10.1016/j.gene.2021.145792

Abstract

Background: Apoptosis is a form of cell death that plays a critical role in the maintenance of tissue homeostasis involving the development and elimination of unwanted cells. Dysregulation of apoptosis appears to be associated in the pathogenesis of many human diseases. Autosomal dominant polycystic kidney disease (ADPKD) is a common monogenetic disease and is mainly caused by mutations in PKD1. Previous studies proved that increased cell death occurred in ADPKD patients and animal models. However, the role of apoptosis in kidney cystogenesis is not clear.

Methods: In current study, due to the high similarities between human and pig, PKD1-deficient (PKD1^+/-) pigs and PKD1-knockdown (PKD1^KD) pig kidney epithelial cells were used to investigate the mechanisms of apoptosis in driving cystogenesis.

Results: In PKD1^+/- pigs, increased intrinsic and extrinsic apoptosis were found at ages of 1 month and 3 months, whereas the autophagy and pyroptosis were not altered. Meanwhile, the intrinsic apoptosis was activated along with untouched extrinsic apoptosis in PKD1^KD pig kidney cells. Thus, the intrinsic apoptosis played important roles in cystogenesis.

Conclusions: This work provides detail analysis of the roles of different cell death types during cystogenesis in ADPKD pig model. The results suggested a potential new strategy for the diagnosis and treatment of ADPKD by targeting intrinsic apoptosis.

Keywords: ADPKD; Intrinsic apoptosis; PKD1; Pig.

MeSH terms

Animals
Apoptosis*
Cell Count
Cell Line
Disease Models, Animal
Gene Knockdown Techniques
Macrophages
Polycystic Kidney, Autosomal Dominant / etiology*
Polycystic Kidney, Autosomal Dominant / genetics
Swine
TRPP Cation Channels / deficiency*
Tumor Necrosis Factor-alpha / metabolism

Substances

TRPP Cation Channels
Tumor Necrosis Factor-alpha
polycystic kidney disease 1 protein