Apoptosis in Polycystic Kidney Disease: From Pathogenesis to Treatment

Zhou, Julie; Li, Yong

doi:10.15586/codon.pkd.2015.ch9

Cited by 18 publications

(22 citation statements)

References 119 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…In addition, epithelial apoptosis is detected during cyst formation (64) and macrophages are known to be professional phagocytes. Thus, resident macrophages may control cyst growth through phagocytosis of damaged epithelial cells and subsequent activation of inflammatory signaling pathways.…”

Section: Resident Macrophage Involvement In Cystic Kidney Diseasementioning

confidence: 99%

Resident Macrophages in Cystic Kidney Disease

Zimmerman

Yoder

2021

Kidney360

View full text Add to dashboard Cite

Interstitial inflammation is an important feature of cystic kidney disease. Renal macrophages are the most well-studied inflammatory cell in the kidney, and their involvement in cyst formation has been reported in different animal models and patients with cystic kidney disease. Originally, it was believed that renal macrophages were maintained from a constant supply of bone marrow–derived circulating monocytes, and could be recruited to the kidney in response to local inflammation. However, this idea has been challenged using fate-mapping methods, by showing that at least two distinct developmental origins of macrophages are present in the adult mouse kidney. The first type, infiltrating macrophages, are recruited from circulating monocytes and gradually develop macrophage properties on entering the kidney. The second, resident macrophages, predominantly originate from embryonic precursors, colonize the kidney during its development, and proliferate in situ to maintain their population throughout adulthood. Infiltrating and resident macrophages work together to maintain homeostasis and properly respond to pathologic conditions, such as AKI, cystic kidney disease, or infection. This review will briefly summarize current knowledge of resident macrophages in cystic kidney disease.

show abstract

Section: Resident Macrophage Involvement In Cystic Kidney Diseasementioning

confidence: 99%

Resident Macrophages in Cystic Kidney Disease

Zimmerman

Yoder

2021

Kidney360

View full text Add to dashboard Cite

show abstract

“…Previously, loss of cystic cells due to apoptosis was shown to reduce PKD progression. 56,57 Effect of ILK on Interstitial Fibrosis, Renal Function, and Survival in PKD Kidneys Pkd1 fl/fl ;Pkhd1-Cre mice develop extensive interstitial damage involving fibrosis and edema, a precursor for collagen deposition and fibrosis. At postnatal (PN) day 25, there was massive fibrosis/edema in Ilk +/+ PKD kidneys with 91% of the interstitial space showing pathologic damage ( Figure 8).…”

Section: Effect Of Ilk On Cystic Diseasementioning

confidence: 99%

Integrin-Linked Kinase Signaling Promotes Cyst Growth and Fibrosis in Polycystic Kidney Disease

Raman

Reif²,

Dai³

et al. 2017

JASN

Self Cite

View full text Add to dashboard Cite

Autosomal dominant polycystic kidney disease (ADPKD) is characterized by innumerous fluid-filled cysts and progressive deterioration of renal function. Previously, we showed that periostin, a matricellular protein involved in tissue repair, is markedly overexpressed by cyst epithelial cells. Periostin promotes cell proliferation, cyst growth, interstitial fibrosis, and the decline in renal function in PKD mice. Here, we investigated the regulation of these processes by the integrin-linked kinase (ILK), a scaffold protein that links the extracellular matrix to the actin cytoskeleton and is stimulated by periostin. Pharmacologic inhibition or shRNA knockdown of ILK prevented periostin-induced Akt/mammalian target of rapamycin (mTOR) signaling and ADPKD cell proliferation Homozygous deletion of ILK in renal collecting ducts (CD) of ; mice caused tubule dilations, apoptosis, fibrosis, and organ failure by 10 weeks of age. By contrast, ; mice had normal renal morphology and function and survived >1 year. Reduced expression of ILK in ; mice, a rapidly progressive model of ADPKD, decreased renal Akt/mTOR activity, cell proliferation, cyst growth, and interstitial fibrosis, and significantly improved renal function and animal survival. Additionally, CD-specific knockdown of ILK strikingly reduced renal cystic disease and fibrosis and extended the life of mice, a slowly progressive PKD model. We conclude that ILK is critical for maintaining the CD epithelium and renal function and is a key intermediate for periostin activation of signaling pathways involved in cyst growth and fibrosis in PKD.

show abstract

“…S1e, f). As dysregulated cell proliferation and apoptosis are key phenotypes of PKD [17][18][19], we next confirmed whether Ift46 has an effect on the alteration of cell proliferation and apoptosis. Increased signals of proliferation markers (Ki-67 and PCNA) and apoptosis marked by TUNEL-positive cells were observed in the cystic kidneys at p21 (Fig.…”

Section: Loss Of Ift46 In the Renal Collecting Duct Causes Pkd Accompanied By Ciliary Defects And Hyper-activates Mapk/erk And Mtor Pathwmentioning

confidence: 73%

Autophagy induction promotes renal cyst growth in polycystic kidney disease

Lee

et al. 2020

EBioMedicine

View full text Add to dashboard Cite

Background Polycystic kidney disease (PKD) involves renal cysts arising from proliferating tubular cells. Autophagy has been recently suggested as a potential therapeutic target in PKD, and mammalian target of rapamycin (mTOR) is a key negative regulator of autophagy. However, the effect of autophagy regulation on cystogenesis has not been elucidated in PKD mice. Methods Clinical validation was performed using GEO datasets and autosomal dominant polycystic kidney disease (ADPKD) patient samples. Newly established PKD and LC3 transgenic mice were used for in vivo verifications, and additional tests were performed in vitro and in vivo using multiple autophagy drugs. Findings Neither autophagy stimulation nor LC3 overexpression alleviated PKD. Furthermore, we observed the inhibitory effect of an autophagy inhibitor on cysts, indicating its possible therapeutic use in a specific group of patients with ADPKD. Interpretation Our findings provide a novel insight into the pathogenesis related to autophagy in PKD, suggesting that drugs related to autophagy regulation should be considered with caution for treating PKD. Funding Sources This work was supported by grants from the Bio & Medical Technology Development Program; the Collaborative Genome Program for Fostering New Post-Genome Industry of the NRF; the Basic Science Program.

show abstract

Apoptosis in Polycystic Kidney Disease: From Pathogenesis to Treatment

Cited by 18 publications

References 119 publications

Resident Macrophages in Cystic Kidney Disease

Resident Macrophages in Cystic Kidney Disease

Integrin-Linked Kinase Signaling Promotes Cyst Growth and Fibrosis in Polycystic Kidney Disease

Autophagy induction promotes renal cyst growth in polycystic kidney disease

Contact Info

Product

Resources

About