Human Kidney Fibroblast: The Heterogeneity of Fibroblasts

A major health issue impacting 9.1% of the world's population is chronic kidney disease (CKD). However, there are still few options for CKD progression prevention. Renal fibrosis, renal anaemia, and peritubular capillary loss are three clinical diseases associated with CKD that are significantly influenced by resident human kidney fibroblast, a type of primary cells. By manufacturing extracellular matrix proteins and erythropoietin under healthy conditions, kidney fibroblasts support the structure of the organ.

Numerous studies have shown that fibroblasts play advantageous functions in the regeneration of renal tubules. In some clinical situations, renal fibroblasts have the capacity to develop into a proinflammatory state, produce a variety of cytokines and chemokines, and extend inflammation by creating tertiary lymphoid tissues, functioning lymphoid aggregates. In this article, we discuss the various roles that renal fibroblasts play in both healthy and pathological states.

Functions of Kidney Fibroblast

The cells known as renal resident fibroblasts are spindle-shaped and found in the interstitium, which is the region between nephrons. The functioning kidney units known as nephrons are made up of glomerular and tubular cells. By creating extracellular matrix (ECM) proteins and interacting with the neighboring cells, fibroblasts support the structural integrity of the kidney and help to keep it in a homeostatic condition in healthy kidneys. Based on their location, morphology, and the positive expression of various fibroblast markers as CD73, it is possible to identify resident fibroblasts. These indicators demonstrate that resident fibroblasts are not expressed negatively by other cell-lineage markers like CD45 because they are neither uniformly positive nor specific for them.

The pericytes

Pericytes, cells derived from mesenchymal stem cells, surround capillaries with processes wrapped in the vascular basement membrane. There are many similarities between resident fibroblasts and pericytes, including their interstitial position and cell surface markers like CD73 and PDGFR, and as a result, these two types of cells are frequently mixed up. With their forceful contractions, pericytes sustain the capillary structure and control vascular tone. They further collaborate with endothelial cells to keep capillary homeostasis.

Renal fibrosis as a defining feature of CKD

Regardless of the origin, renal fibrosis is a prevalent pathological feature of CKD. It is known as a predictive indication of renal prognosis and is characterised as a caused by accumulation of ECM, such as collagen and fibronectin, in the interstitium. Previous research has demonstrated that the renal fibroblasts' failure can lead to a number of clinical diseases connected to CKD, including renal fibrosis, renal anaemia, and peritubular capillary loss. In light of this, research on renal fibroblasts as potential therapeutic targets for CKD and related consequences has gained attention.

Concluding Remarks

In order to maintain homeostasis under physiological circumstances, resident fibroblasts in the kidney are crucial components. Renal fibrosis, renal anaemia, and peritubular capillary loss are the three primary pathological abnormalities in CKD that are brought on by malfunction of the renal fibroblasts. It is significant to note that renal fibroblasts are diverse and can alter their morphologies in response to the local microenvironment. Renal fibroblasts can develop into proinflammatory fibroblasts that release inflammatory cytokines and chemokines, promoting TLT development in a variety of pathological circumstances. Through the expression of CD73, fibroblasts or pericytes also have an anti-inflammatory effect.

A novel therapeutic strategy for kidney conditions may be developed with a better understanding of the variability and functions of renal fibroblasts. The variability of renal fibroblasts, which had not previously been recognised by traditional technologies, has recently been shown by innovative technologies such scRNA-seq. It is anticipated that the application of these technologies to a range of clinical renal disorders would further illuminate the variability of renal fibroblasts, leading to a better knowledge of the pathophysiology of kidney diseases and the creation of innovative therapeutic approaches.