Defining therapeutic targets for renal fibrosis: Exploiting the biology of pathogenesis.

Biomed Pharmacother

Center for Drug Safety Evaluation and Research of Zhejiang University, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China. Electronic address:

Published: November 2021

Renal fibrosis is a failed wound-healing process of the kidney tissue after chronic, sustained injury, which is a common pathway and pathological marker of virtually every type of chronic kidney disease (CKD), regardless of cause. However, there is a lack of effective treatment specifically targeting against renal fibrosis per se to date. The main pathological feature of renal fibrosis is the massive activation and proliferation of renal fibroblasts and the excessive synthesis and secretion of extracellular matrix (ECM) deposited in the renal interstitium, leading to structural damage, impairment of renal function, and eventually end-stage renal disease. In this review, we summarize recent advancements regarding the participation and interaction of many types of kidney residents and infiltrated cells during renal fibrosis, attempt to comprehensively discuss the mechanism of renal fibrosis from the cellular level and conclude by highlighting novel therapeutic targets and approaches for development of new treatments for patients with renal fibrosis.

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.biopha.2021.112115DOI Listing

Publication Analysis

Top Keywords

renal fibrosis
28
renal
11
therapeutic targets
8
fibrosis
7
defining therapeutic
4
targets renal
4
fibrosis exploiting
4
exploiting biology
4
biology pathogenesis
4
pathogenesis renal
4

Similar Publications

Objective: Elevated systolic blood pressure and increased pulse pressure are closely associated with renal damage; however, the exact mechanism remains unclear. Therefore, we investigated the effects of increased pulse pressure on tubulointerstitial fibrosis and renal damage in elderly rats with isolated systolic hypertension (ISH). Additionally, the role of renal tubular epithelial-mesenchymal transition (EMT) and its upstream signalling pathways were elucidated.

View Article and Find Full Text PDF

Background: Hyperuricemia (HUA) is a condition characterized by excessive uric acid production and/or inadequate uric acid excretion due to abnormal purine metabolism in the human body. Uric acid deposits resulting from HUA can lead to complications such as renal damage. Currently, drugs used to treat HUA lack specificity and often come with specific toxic side effects.

View Article and Find Full Text PDF

The mineralocorticoid receptor (MR) is a nuclear transcription factor that plays a critical role in regulating fluid, electrolytes, blood pressure, and hemodynamic stability. In conditions such as chronic kidney disease (CKD) and heart failure (HF), MR overactivation leads to increased salt and water retention, inflammatory and fibrotic gene expression, and organ injury. The MR is essential for transcriptional regulation and is implicated in metabolic, proinflammatory, and pro-fibrotic pathways.

View Article and Find Full Text PDF

Immunoglobulin G4-related disease (IgG4-RD) and systemic lupus erythematosus (SLE) are multisystemic autoimmune disorders that can present with renal manifestations. Overlapping cases of these diseases are extremely rare and present both diagnostic and therapeutic challenges. We report the case of a 70-year-old male with a history of autoimmune pancreatitis, who was admitted with fatigue, weight loss, and worsening kidney function.

View Article and Find Full Text PDF

In glomerulopathies, endothelial dysfunction and the presence of histological vascular lesions such as thrombotic microangiopathy, arteriolar hyalinosis, and arteriosclerosis are related to a severe clinical course and worse renal prognosis. The endothelial cell, which naturally has anti-inflammatory and anti-thrombotic regulatory mechanisms, is particularly susceptible to damage caused by various etiologies and can become dysfunctional due to direct/indirect injury or a deficiency of protective factors. In addition, endothelial regulation and protection involve participation of the complement system, factors related to angiogenesis, the renin-angiotensin system (RAS), endothelin, the glycocalyx, the coagulation cascade, interaction between these pathways, interactions between glomerular structures (the endothelium, mesangium, podocyte, and basement membrane) and interstitial structures (tubules, arterioles and small vessels).

View Article and Find Full Text PDF

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!